essay science in the service of man

Science in the Service of Man Essay with Quotations

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Science is an unending search for truth. It has proved a faithful friend of mankind. It has increased human comfort.

Life is a struggle. The man has to work throughout his life. It is the science that helps him to make a safe home for him. Now there is no need to live in the caves. The man has built magnificent buildings. The houses are full of facilities. Science has made human life very comfortable and safe.

In the past man had to travel on foot. Now travel has become a pleasure for him. It is no more difficult and dangerous. Trains, buses, cars and taxies all are available to serve us. Man is not sad at saying goodbye to this near ones. He can contact them easily on the telephone and mobiles. All this is possible because of science.

Science has provided us with many means of information, entertainment and fun. TV, Radio and Computers all are sure means of entertainment. The computer has changed the world into a global village.

Wonderful drugs cure the man of diseases. Science has reached its highest point in the field of surgery.

In short, science is a great blessing of God to mankind. Even it has broadened our outlook and views. Now we think in a broader sense.

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Spelling mistake In short science is a great blessing of God to mankind but there’s a mistake of God spelling

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> Science and Human Experience
> Can Science Serve Mankind?

Book contents

Frontmatter
Acknowledgement
Part One Science and Society
1 Science and Human Experience: (Mephistopheles Is Alive and Well and Living in the Space Age)
2 Does Science Undermine our Values?
3 Can Science Serve Mankind?
4 Modern Science and Contemporary Discomfort: Metaphor and Reality
5 Faith and Science
6 Art and Science
7 Fraud in Science
8 Why Study Science? The Keys to the Cathedral
9 Is Evolution a Theory? A Modest Proposal
10 The Silence of the Second
11 Introduction to Copenhagen
12 The Unpaid Debt
Part Two Thought and Consciousness
Part Three On the Nature and Limits of Science

3 - Can Science Serve Mankind?

from Part One - Science and Society

Published online by Cambridge University Press: 05 November 2014

The naïve scientific optimism of the nineteenth century has been replaced by cynicism regarding the ability of science to serve mankind. Some blame science for the breakdown of the social order of an idealized past. Does science serve mankind, or does mankind serve science?

This essay is based on a talk given at the opening ceremony of the conference “Science in the Service of Mankind,” Vienna, Austria, July 8-14, 1979 .

The scientific optimist who wrote in the 1808 Elements of Natural Philosophy : “The great object of science is to ameliorate the condition of man, by adding to the advantages which he naturally possesses,” is no longer with us. He has been replaced by the environmentalist, the conservationist, the consumer advocate, and the professional demonstrator who criticize every aspect of science and most other human activities – who, regarding the splendor of this gathering and the obvious prosperity of its participants, might suggest that the appropriate question is: Can mankind afford to continue to serve science?

As is evident from the topics covered in this conference, in a material sense science has provided, and continues to provide, solutions for many problems. It is obvious that life as we have come to expect it would not be possible without the material fruits of science.

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Can Science Serve Mankind?
Leon N. Cooper , Brown University, Rhode Island
Book: Science and Human Experience
Online publication: 05 November 2014
Chapter DOI: https://doi.org/10.1017/CBO9781107337879.005

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Essay On Science In The Service Of Man

Post category: Essay
Reading time: 5 mins read

The modern age has rightly been mentioned as the Age of Science. Science has unlocked and widened the new boundaries of human knowledge, information, comforts and achievements. The scientific path from unawareness to knowledge, from superstitions to scientific wisdom and from darkness to light, has been a long struggle. This struggle was full of troubles, determination, labour, hardwork, trial and errors as well as challenges.

Man’s hunger for knowledge has resulted in remarkable progress of science in different societies. Science is universal, complete, simple and yet very complex. It includes reasoning, analysing and systematic study of various things. Science has helped man to conquer different things. Now, the moon is within the man’s reach and planets are not too far off from his observation and study.

Satellite communication has helped in rapid contact of people from one corner of the world to another. Immediate communication through telephones, mobiles and electronic mails great wonders of science. Through networking, a computer can be connected to other computer in are the world. Satellites have also changed the world of entertainment through radios and cable televisions. Science has completely changed the viewpoint of man.

The scientific ride is wonderful, pleasant and thrilling Man’s life has become easy, convenient and comfortable because of several scientific inventions. Science is a powerful weapon and it is up to man how to uses it. It is neither a boon nor a curse. However, it is in the hands of man to decide what service he desires from science. Thus, it is unwise to categories science as an evil or good.

Science is a knowledge, a power, a blessing and a a key to solve the different secrets of nature. It has helped us in getting rid of many deadly diseases. Now-a-days transplantation of human organs is a common medical practice. Due to many medical discoveries and progresses, man finds himself safer and protected. Moreover, his lifespan has also extended.

The miracles and achievements of science are too many. It has helped man to jump into a comfortable world of successes and luxuries. No doubt the misuse of science and its discoveries has brought the entire humanity on the edge of destruction. It has produced destructive weapons, like nuclear bombs, missiles, deadly gases, etc. Thus, science should be used as a benefit, as a means and a tool to improve the quality of life. The misuse and abuse of science are bound to make our life horrifying.

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Science in the service of man | english essay for second year.

Science in the Service of Man | English Essay

Albert Einstein, a German-born U.S. physicist says:

Knowledge resembles a statue of marble which stands in the desert and is continuously threatened with burial by the shifting sands. The hands of science must ever be at work in order that the marble column continues everlastingly to shine in the sun.

Thus science is a persistent pursuit of knowledge, skill, and enlightenment. It reveals sheer truths, mere facts, and bare realities of the universe. It is based on an observation of the fundamental laws of nature. Through its permanent quest, it has opened up new and novel horizons of discovery and invention.

Its enormous impact on agriculture, industry, medicine, astronomy, navigation and traveling is exceedingly amazing. It has proved to be the most trusted and entertaining friend of humanity. It has doubled and multiplied human efficiency and comfort with its vast range of applications and innumerable inventions.

It is human nature to explore new horizons of nature. Man explores the undiscovered and unseen recesses of nature to satiate his unquenched thirst for knowledge. Man will always continue to discover the secret aspects of the cosmos. And it is the science that helps man to accomplish such pursuits.

Life is a constant struggle for survival where man has to toil unceasingly to provide himself with the basic facilities of life. In the past, man had to sweat blood to meet his simple needs. His life was quite uncertain and unsafe. He had to struggle for food, shelter, and security. He had to defend himself against the wild beasts and the odds of life.

Now he has invented powerful weapons to defend himself and his country. With the help of science, he has succeeded in securing a safe home. There is no need for digging holes in the earth to live. Man has built skyscrapers and graceful buildings for this purpose. Even in the house, a woman needs not work with her hands.

She has a spacious decorated house, a well-furnished kitchen, and numerous pieces of equipment to do her domestic duties. As far as food is concerned, man grows all kinds of crops and vegetables throughout the year. He is no more afraid of hunger and famine.

He has invented huge and reliable machines to perform his task in the fields. These machines do their work with magical quickness and accuracy. All this has become possible due to science.

Bertrand Russell, in his book, ‘A History of Western Philosophy’ says:

Almost everything that distinguishes the modern world from earlier centuries is attributable to science.

In the past, man had to travel on foot. Now travel has become a pleasure for him. Swift and speedy means of travel are easily available. He can travel around the world just for pleasure. He had got the better of birds in flight.

He is no more grieved to say goodbye to his relatives and friends. He can meet them and visit them whenever he likes. He has invented more speedy airplanes than sound. By then, he can cover long distances in the twinkling of an eye.

Aeroplanes, trains, buses, and cars are to carry him anywhere across the country. All these quick means of transportation are the result of science. Probably it was this kind of travel about which John Keats once said:

Ever let the fancy roam, pleasure never is at home.

Science has provided us with many means of information, entertainment, amusement, and fun. TV, Radio, VCR, Dish antenna, Cinema, and Computers all are sure means of entertainment and recreation.

The computer and other prompt means of communication have converted the whole world into a global village. Now man can enjoy any sort of extravaganza at any time and at any place.

He can enjoy an activity being performed thousands of miles away around the world. Science has performed wonders in the field of medicine. Diseases like tuberculosis, smallpox, and cholera are no more fatal and deadly. Now plague and epidemics have been controlled. Wonderful drugs have been discovered to the man of pain and diseases.

Antiseptics can kill the germs that spread diseases. The most bewildering achievement of science in this regard is that it has given man a scientific outlook and rational approach to comprehending the mystic of nature. In the field of surgery, science is touching the zenith of progress. Walt Whitman, a U.S poet recites:

Of physiology from top to toe I sing. (Leaves of grass, ‘I Sing the Body Electric)

In short, science is a great blessing which has proved to be useful in all fields of life. It has brought all the nations on one Platform, This age of illumination is different from the age of darkness only because of science. Science has even enlightened us spiritually as it has broadened our views and outlook. We have begun to perceive the laws and the phenomena of nature adequately.

Anila Ibrahim

An educationist, web content writer, equipped with an LLB and a Master’s degree in English Literature, as well as a Master of Philosophy in Entrepreneurship. I have a comprehensive understanding of both the English language and the educational landscape. This academic background empowers Anila to deliver content that is not only informative but also thoroughly researched.

21 thoughts on “ Science in the Service of Man | English Essay for Second Year ”

Good Essay maam!

Thnku mam g

Science is very important in our life.it is very informative essay

Thank you mam

Good morning mam Assalam o Alaikum

JzakAllah mam Good Essay mam.

Good job mam

Excellent…..

That's true.science plays important role in or lives

Secret aspect of the Cosmos mean??

Excellent, easy, meaningful and very informative for us

Mam g essyy bht lenthy h

Thnku so much mam g it's so informative essay

It means the secret ways of univerrse

It's prepared for outstanding students

Thanks Mam,essy so good and informative but very lenty

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This I Believe

An ideal of service to our fellow man.

Albert Einstein

Listen to Robert Krulwich Read Einstein's Essay

Albert Einstein published his general theory of relativity in 1916, profoundly affecting the study of physics and cosmology for years. He won the Nobel Prize for Physics in 1921 for his work on the photo-electric effect. Einstein taught for many years at the Institute for Advanced Study at Princeton. Yousef Karsh hide caption

NPR's Robert Krulwich. hide caption

NPR's Robert Krulwich reads Albert Einstein's This I Believe essay, which first aired circa 1954.

The most beautiful thing we can experience is the Mysterious — the knowledge of the existence of something unfathomable to us, the manifestation of the most profound reason coupled with the most brilliant beauty. I cannot imagine a God who rewards and punishes the objects of his creation, or who has a will of the kind we experience in ourselves. I am satisfied with the mystery of life's eternity and with the awareness of — and glimpse into — the marvelous construction of the existing world together with the steadfast determination to comprehend a portion, be it ever so tiny, of the reason that manifests itself in nature. This is the basis of cosmic religiosity, and it appears to me that the most important function of art and science is to awaken this feeling among the receptive and keep it alive.

I sense that it is not the State that has intrinsic value in the machinery of humankind, but rather the creative, feeling individual, the personality alone that creates the noble and sublime.

Man's ethical behavior should be effectively grounded on compassion, nurture and social bonds. What is moral is not the divine, but rather a purely human matter, albeit the most important of all human matters. In the course of history, the ideals pertaining to human beings' behavior towards each other and pertaining to the preferred organization of their communities have been espoused and taught by enlightened individuals. These ideals and convictions — results of historical experience, empathy and the need for beauty and harmony — have usually been willingly recognized by human beings, at least in theory.

The highest principles for our aspirations and judgments are given to us westerners in the Jewish-Christian religious tradition. It is a very high goal: free and responsible development of the individual, so that he may place his powers freely and gladly in the service of all mankind.

The pursuit of recognition for their own sake, an almost fanatical love of justice and the quest for personal independence form the traditional themes of the Jewish people, of which I am a member.

But if one holds these high principles clearly before one's eyes and compares them with the life and spirit of our times, then it is glaringly apparent that mankind finds itself at present in grave danger. I see the nature of the current crises in the juxtaposition of the individual to society. The individual feels more than ever dependent on society, but he feels this dependence not in the positive sense — cradled, connected as part of an organic whole. He sees it as a threat to his natural rights and even his economic existence. His position in society, then, is such that that which drives his ego is encouraged and developed, and that which would drive him toward other men (a weak impulse to begin with) is left to atrophy.

It is my belief that there is only one way to eliminate these evils, namely, the establishment of a planned economy coupled with an education geared towards social goals. Alongside the development of individual abilities, the education of the individual aspires to revive an ideal that is geared towards the service of our fellow man, and that needs to take the place of the glorification of power and outer success.

Translation by David Domine. Essay courtesy of the Albert Einstein Archives at The Hebrew University of Jerusalem.

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English Essay on “Science in The Service of Man” English Essay-Paragraph-Speech for Class 8, 9, 10, 11 and 12 CBSE Students and competitive Examination.

Science in The Service of Man

Essay No. 01

Science has brought a transformation in the man’s entire lifestyle. We do every work with the help of science. Even the most ordinary things we use in this modern age is the result of invention of science. A lead pencil, a pen or a book is the product of science.

Science has conquered time and distance. The world has become a smaller place due to the development of means of transportation. The railway engine was invented more than a century before. It replaced the bullock cart. We can travel from one part of the country to another. A great improvement has been made in the railways. An aeroplane can take us to the remotest corner of the globe in a few hours. Now man, can fly at about 4000 miles per hour. Space flights have become very common in the U.S.A. and the U.S.S.R. They have landed on the Moon and Mars. This has been man’s greatest adventure in space.

In domestic life we use filtered water, electric light, radio, television and telephone. We just have to put on the switch to iron our clothes, to generate electricity, to put on the water heater fan, coolers, air conditioners etc. We have many other inventions of science for our domestic use. Electric iron, toaster and heater are in common use. We can talk to our friends and customers on telephone. It takes a few seconds to connect with the other end. Television is the most modern achievement of science. It is a combination of radio and cinema. What a wonderful piece of work the man has produced. The use of atomic energy is another wonder of science.

The finest cloth is produced for men and women: All the necessities and luxuries are produced by machines. We get all amenities of life. Machine can produce more and more. Computers are the latest wonder of science. Computer does the job of hours in minutes.

Essay No. 02

Science has made great strides during the twentieth century. It is regarded as the age of science. Science is making speedy achievements in one sphere or the other in one part of the world or another. Whether on land, sea or in space, science has made great achievements. It has made a lot of progress in space. It has made possible man’s landing on the moon. In a man’s life, science plays a very important role. All our gadgets of comfort available in the household are the gifts of science. Television, VCR, radio, air-conditioners, fans, etc. are all boons of science. Science is also a source of destruction. The modern warfare, with the help of science, is deadly and devastating. The havoc caused by the atom bomb in Hiroshima and Nagasaki is beyond description. Science, if used in the right direction, can render a very good service to mankind. It is necessary that science should be used in the right direction so that it can make human life more comfortable. Science is a good slave but a bad master.

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Essay on Science In The Service of Man

Essay on Science In The Service of Man: Science has revolutionized the way we live our lives, making it easier, faster, and more convenient. From medical advancements to technological innovations, science has truly been in the service of man. In this essay, we will explore the various ways in which science has improved our lives and how it continues to shape our future. Join us as we delve into the fascinating world of science and its impact on society.

Table of Contents

Science In The Service of Man Essay Writing Tips

1. Introduction: Start your essay by introducing the topic of science and its importance in serving mankind. Mention how science has revolutionized the way we live and has contributed to the betterment of society.

2. Define the role of science: Explain the role of science in solving various problems faced by humanity. Mention how scientific advancements have led to improvements in healthcare, agriculture, communication, transportation, and other fields.

3. Discuss the impact of science on healthcare: Highlight the contributions of science in the field of medicine and healthcare. Mention how advancements in medical technology, research, and treatments have improved the quality of life and increased life expectancy.

4. Explain the role of science in agriculture: Discuss how science has revolutionized agriculture and food production. Mention how scientific innovations such as genetically modified crops, pesticides, and irrigation techniques have increased crop yields and helped in feeding a growing population.

5. Discuss the impact of science on communication and technology: Explain how science has transformed communication and technology. Mention how inventions such as the internet, smartphones, and social media have revolutionized the way we communicate and access information.

6. Highlight the role of science in environmental conservation: Discuss how science has played a crucial role in understanding and addressing environmental issues. Mention how scientific research has led to the development of sustainable practices and technologies to protect the environment.

7. Discuss the importance of scientific research and innovation: Highlight the significance of scientific research and innovation in driving progress and development. Mention how investment in scientific research leads to new discoveries, inventions, and solutions to complex problems.

8. Conclusion: Summarize the key points discussed in the essay and emphasize the importance of science in serving mankind. Mention how science continues to play a crucial role in improving the quality of life and addressing global challenges. Encourage readers to appreciate and support scientific advancements for the betterment of society.

Essay on Science In The Service of Man in 10 Lines – Examples

1. Science has revolutionized the way we live, making our lives easier and more comfortable. 2. It has helped in the advancement of medicine, leading to the development of life-saving drugs and treatments. 3. Science has also improved agriculture, increasing crop yields and ensuring food security for millions. 4. It has played a crucial role in the field of communication, enabling us to connect with people around the world instantly. 5. Science has led to the development of technology that has transformed industries and created new job opportunities. 6. It has helped in the conservation of natural resources and the protection of the environment. 7. Science has enabled us to explore outer space, uncovering the mysteries of the universe. 8. It has enhanced our understanding of the world around us, leading to new discoveries and innovations. 9. Science has improved the quality of life for people across the globe, making healthcare more accessible and affordable. 10. Overall, science has been instrumental in improving the well-being of humanity and shaping the world we live in today.

Sample Essay on Science In The Service of Man in 100-180 Words

Science has played a crucial role in improving the quality of human life. From advancements in medicine that have led to the eradication of deadly diseases to technological innovations that have made communication and transportation faster and more efficient, science has truly been in the service of man.

One of the most significant contributions of science to society is the development of vaccines and antibiotics, which have saved countless lives and prevented the spread of infectious diseases. Additionally, advancements in agriculture have led to increased food production, ensuring that people have enough to eat.

Furthermore, science has revolutionized the way we live and work through the invention of computers, smartphones, and the internet. These technologies have made information more accessible and communication more convenient.

In conclusion, science has undoubtedly been a powerful force for good in the world, improving the lives of people in countless ways. It is essential that we continue to support and invest in scientific research to further harness its potential for the benefit of humanity.

Short Essay on Science In The Service of Man in 200-500 Words

Science has played a crucial role in shaping the world we live in today. From advancements in technology to medical breakthroughs, science has truly been in the service of man. The impact of science on society cannot be overstated, as it has revolutionized the way we live, work, and communicate.

One of the most significant ways in which science has served mankind is through the development of technology. The invention of the wheel, the printing press, and the internet are just a few examples of how science has improved our lives. Technology has made it easier for us to communicate with one another, travel long distances, and access information at our fingertips. Without science, we would not have the smartphones, computers, and other gadgets that have become an integral part of our daily lives.

In addition to technology, science has also played a crucial role in the field of medicine. The discovery of antibiotics, vaccines, and other medical treatments has saved countless lives and improved the quality of life for millions of people around the world. Thanks to science, we have been able to eradicate diseases such as smallpox and polio, and continue to make progress in the fight against cancer and other deadly illnesses. The field of genetics has also made great strides in recent years, allowing us to better understand and treat genetic disorders.

Furthermore, science has also had a significant impact on the environment. Through advancements in renewable energy sources, such as solar and wind power, scientists have helped to reduce our dependence on fossil fuels and mitigate the effects of climate change. Additionally, research in conservation biology has helped to protect endangered species and preserve biodiversity for future generations. Without science, we would not have the knowledge or tools necessary to address the environmental challenges facing our planet.

In conclusion, science has truly been in the service of man, improving our lives in countless ways. From technology to medicine to environmental conservation, the impact of science on society is undeniable. As we continue to make advancements in scientific research and innovation, it is important to remember the importance of supporting and investing in science for the betterment of humanity. By harnessing the power of science, we can continue to make progress and create a brighter future for all.

Essay on Science In The Service of Man in 1000-1500 Words

Science has played a crucial role in shaping the world we live in today. From advancements in technology to medical breakthroughs, science has truly been in the service of man. Throughout history, scientists have dedicated their lives to understanding the world around us and using that knowledge to improve the quality of life for humanity. In this essay, we will explore how science has benefited mankind in various aspects of life.

One of the most significant ways in which science has served man is through the field of medicine. The advancements in medical science have led to the development of vaccines, antibiotics, and various treatments for diseases that were once considered incurable. Diseases such as smallpox, polio, and tuberculosis have been eradicated or significantly reduced in prevalence due to the efforts of scientists and medical professionals. The discovery of antibiotics, such as penicillin, has revolutionized the treatment of bacterial infections and saved countless lives.

In addition to treating diseases, science has also made significant progress in preventing them. Vaccines have been developed to protect against a wide range of infectious diseases, including measles, mumps, rubella, and influenza. These vaccines have helped to prevent outbreaks of these diseases and have saved millions of lives. The development of vaccines has also played a crucial role in the fight against deadly diseases such as Ebola and Zika virus.

Furthermore, science has also contributed to the field of surgery and medical procedures. Advances in surgical techniques, anesthesia, and medical imaging have made surgeries safer and more effective. Minimally invasive procedures, such as laparoscopic surgery, have reduced recovery times and improved patient outcomes. Medical imaging technologies, such as MRI and CT scans, have enabled doctors to diagnose and treat diseases with greater precision.

Another area where science has served man is in the field of technology. The development of computers, smartphones, and the internet has revolutionized the way we communicate, work, and access information. These technological advancements have made our lives more convenient and efficient. The internet has connected people from all over the world and has provided access to a wealth of information at our fingertips. Computers have enabled us to perform complex calculations, analyze data, and create simulations that were once impossible.

Moreover, science has also played a crucial role in the field of transportation. The invention of the steam engine, automobiles, airplanes, and trains has made travel faster, safer, and more accessible. These advancements have connected people and cultures from different parts of the world and have facilitated trade and commerce. The development of electric cars and public transportation systems has also helped to reduce carbon emissions and combat climate change.

Furthermore, science has contributed to the field of agriculture and food production. The development of fertilizers, pesticides, and genetically modified crops has increased crop yields and improved food security. These advancements have helped to feed a growing global population and reduce hunger and malnutrition. In addition, science has also led to the development of sustainable farming practices that protect the environment and preserve natural resources.

In conclusion, science has truly been in the service of man in various aspects of life. From advancements in medicine to technology, transportation, agriculture, and food production, science has improved the quality of life for humanity. Scientists and researchers continue to push the boundaries of knowledge and innovation to address the challenges facing our world today. It is essential that we continue to support and invest in scientific research to ensure a better future for generations to come.

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Science Is The Service Of Man (Essay Sample)

“Truth”, is the original meaning of the word which the word Science came from. It is common knowledge that all this time scientist have been chasing the knowledge explained and expounded by the scientific method because they believe that science is a field of study that never depends on opinion thus, regards only a certain one true idea in a certain framework. And this science, is profound to be the service of man in many years even before.

Science have been incorporated to another technical term or the ‘technology’. Technology is the actual application and product being develop by years of study of scientist in their theories then applied in laboratory for test. Science and technology have been existing far beyond the early age of man. It was science when the early man understood the use of fire in order to survive and also when they improve their life using stick and stone. In the preceding years, when man’s civilization was improved, one of the ground for improvements they focus on is science and learning it is because they understood that in order to further improve their society and gain advantage against their enemies they need to have better understanding of resources available to them. Science is the service of man in many terms such as in education, health, and technology. Education is an essential part of social system because it enables the young ones gain learning and proper training in order to engage to the problem that the communities are facing. The role of science in education system kicks-in in the form of academic subject that is divided on different category like general science, biology, chemistry and physics. The following general science topics have been greatly discussed in education, mainly because those topics are the basic ideas that one should know in order to move on intermediate or advance level of learning. Also, these science fields opens the perspective of many people that leads to many discovery and as we all know the living proof of science, as being service to the man, are very obvious around us because our clothes, chair, flooring, walls, gadgets, electricity and over-all most of what we use in daily basis are explained, studied and improved by science. Also, science have been service of man when it comes to health issues. Without science, there would be catastrophe and low mortality rate because mankind have faced a lot of sickness in many degrees like pandemic and epidemic level. Example of this sickness is the widely known as Black plague that claims thousands of lives, but humanity stood still and found the cure of the disease and even if we faced the new generation of sickness we have still been able to find solution on how to cure them, Moreover, science have been proven itself on technology side when it comes on developing the communication, transportation and human understanding of environment and human nature itself. Science, based upon on current news and events, have put mankind into another milestone, as it opens the digital age. In digital age, science have applied its theories into practical application making the gadgets of today fast and reliable like the wireless handset we used in communication and the upgrade of transportation that we used like the vehicles, trains, ships and airplanes.

To sum it up, it once said that ‘necessity is the mother of all invention’, it is without a doubt, that we humans are changing and the things we need also need to cope up on our needs and for us to get our hands on things we need there is the science that will be service to the man.

SCIENCE AND TECHNOLOGY IN THE SERVICE OF MAN

October 2023

Federal University of Technology Owerri

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National Academy of Sciences (US) Committee on Research in the Life Sciences. The Life Sciences: Recent Progress and Application to Human Affairs: The World of Biological Research Requirements for the Future. Washington (DC): National Academies Press (US); 1970.

The Life Sciences: Recent Progress and Application to Human Affairs: The World of Biological Research Requirements for the Future.

Hardcopy Version at National Academies Press

CHAPTER TWO BIOLOGY IN THE SERVICE OF MAN

Progress in biological understanding has proceeded at a spectacular rate for two decades. The deepening insights into the nature of man and his diverse living kin could well be reward enough for the large investment of effort and funds. Such understanding is more than a highlight of our culture; it is a primary tool of our working civilization. In the pages that follow we shall seek to illustrate and document that statement. Only a small sampling can be offered here, but it should become evident that the life sciences have dramatically altered our life style, contributing to our security, our health, our comfort, and our enjoyment.

BIOLOGICAL RESEARCH AND MEDICAL PRACTICE

The impressive and rapidly growing, though fragmentary, conceptual structure of biology has greatly increased understanding of disease mechanisms; presumably, as the conceptual framework becomes more general and more coherent, comprehension of disease will grow correspondingly, thereby enlarging opportunity for the alleviation and prevention of many disorders. In considerable measure, the history of biology is the history of attempts to cope with disease. Many disorders have fruitfully been viewed as “nature's experiments” and, as such, have proved to be cardinal clues in elucidation of major fundamental phenomena. Thus, vitamin-deficiency diseases—e.g., pellagra, beriberi, sprue, and scurvy—were the clues to the very existence of vitamins and, hence, to the coenzymes of metabolism; investigations of diabetes and glycogen-storage diseases revealed the hormonal control of carbohydrate metabolism and, indeed, the pathways of that metabolism; the prevalence of pernicious anemia revealed the existence of vitamin B 12 and of the unique biochemical reactions it makes possible; the requirement for agents to manage infectious diseases stimulated the discovery of antibiotics, and these, in turn, proved to be powerful tools in the elucidation of the mechanism of operation of the genetic apparatus and the synthesis of bacterial cell walls; the dramatic changes in the volume, pH, and salt concentrations of blood plasma in such disorders as infantile diarrhea, pernicious vomiting, diabetic coma, and Addison's disease have been both the primary stimuli and the major “experiments” in revealing the complex homeostatic mechanisms that control the volume, acidity, and electrolyte composition of the body fluids of both the intracellular and extracellular compartments; the variety of cardiac disorders has revealed the fine mechanisms and neural control of the cardiovascular system; and the existence of sickle cell anemia and other instances of altered hemoglobin structure were the first demonstration that a “point” mutation results in a specific amino acid replacement in a protein, as well as the demonstration that the genetic code in man must be identical with that in the bacterial species in which it was first determined. In each instance, the knowledge so gained, abetted by insights from other areas of biology, has resulted in expansion and improvement of the therapeutic armamentarium to the great benefit of those afflicted with the very disorders that served as clues.

This mutual feedback has characterized much biomedical practice. Advances in practice have come only when the intellectual stage was set and suitable methods were in hand. Painstaking analyses of the electrolyte composition of the blood in health and disease, over a period of 40 years, contributed much to current understanding. But the analytical methods required were tedious, slow, and unreliable in the hands of any but highly qualified experts. In the last decade, these were replaced by a variety of thoroughly reliable, semiautomated procedures, allowing the benefits of this understanding to be brought to virtually all those requiring it. The precise control thus afforded, symbolized in the bottles of intravenous infusions so common in modern hospital practice, has dramatically reduced mortality in a variety of illnesses and has been a major contribution to the success of current heroic surgical procedures. Hence, one no longer encounters the once painfully exact irony, “The operation was successful but the patient died.” The new analytical methods and their use in guiding parenteral fluid therapy are the fruit of thousands of painstaking investigations. This chapter cannot hope to provide a comprehensive summary of such contributions but will, rather, describe a few recent noteworthy illustrations.

The National Health

The dramatically altered national health picture since the turn of the century broadly illustrates the changes man has wrought through his science and suggests those yet to be accomplished. Fifty years ago the major medical problems afflicting individuals in the United States were similar to those now facing developing nations. In 1900, both influenza and pneumonia killed more persons than any other disease. Tuberculosis came next. The combined death rate (deaths per 100,000 of population) from these diseases was greater than that from heart disease today, a malady that killed more than 712,000 persons in 1965, when cancer took the lives of an additional 300,000 individuals. In the early 1900's, the death rate from tuberculosis exceeded that from either of these causes, while diphtheria, now almost unknown, was the tenth leading cause of death. For three decades, pellagra —deficiency of the vitamin nicotinic acid—was the leading cause of death in eight southeastern states, whereas cases of this disease have rarely been reported since 1945, and mortality is zero.

Diagnosis, Disease, and Drugs

Sulfonamides and antimetabolites.

Quite evidently, many people who would have succumbed to infectious disease in an earlier day now survive to die, at a later age, of degenerative disease or cancer. The advent of antibiotics deserves major credit for current ability to cope with infections. Moreover, antibiotics have played a major role in the development of drugs and approaches to the treatment of other diseases, including cancer, by illuminating the broad principle of drug design, which is fundamental to much current research.

From understanding of the mechanism by which sulfonamides inhibit the growth of bacteria came the concept of antimetabolites and new insights into the essential relationship between molecular form and physiological function. Simply stated, an antimetabolite inhibits the activity of an enzyme that cells need for growth or other normal activity because it closely resembles the natural substrate of that enzyme. However, the antimetabolite cannot be affected by the enzyme and remains attached to its surface; in consequence, the enzyme cannot perform its normal function. The discovery of specific bacterial inhibition has a long history. In 1904, Paul Ehrlich, a German scientist, postulated that infectious diseases could be treated if chemicals could be found with a greater affinity and toxicity for parasite organisms than for host cells. Using dyes against trypanosomes and arsenicals against spirochetes, he demonstrated the validity of his hypothesis and provided the earliest useful treatment for syphilis. In 1935, a dye called Prontosil was shown to be effective in treating streptococcal infections in patients, though it had no effect on bacteria in a test tube. The demonstration that individuals treated with Prontosil excrete sulfanilamide, a degradation product of the dye in the body, was soon followed by observation that this compound inhibits both infection in patients and the growth of organisms in laboratory test media. A vigorous program of chemical modification of the basic structure led to a new class of drugs, the sulfonamides. Even now, these are the drugs of choice in the treatment of gastrointestinal and urinary-tract infections.

Early empirical success with sulfanilamide rendered it imperative that the mechanism of its effect be understood, so as to permit design of even more effective congeners. A-lengthy series of observations, conducted in a multitude of laboratories at home and abroad, yielded the following conclusions:

Sulfonamides inhibit bacterial growth by preventing the organisms from synthesizing folic acid, a vitamin for man, lack of which results in sprue. Normal synthesis of folic acid by bacteria and plants commences with the incorporation of p-aminobenzoic acid. In molecular structure, p-aminobenzoic acid and the sulfonamides are distinctly similar.

When a sulfonamide attaches itself to the enzyme responsible for the normal reaction with p-aminobenzoic acid, synthesis is blocked, and, for lack of folic acid, the bacterium cannot survive. Because man is unable to synthesize his own folic acid, the sulfonamides do his metabolism no harm, selectively attacking bacteria while leaving human cells undamaged. It was these observations that gave rise to the concept of antimetabolite drugs. Many have since been usefully synthesized, but no better example of the concept is yet available.

ANTIBIOTICS

Penicillin was discovered in 1929 when a British bacteriologist observed the inhibitory properties of the fungus Penicillium notatum, which secretes penicillin into surrounding media. This substance, destined to become the most widely used antibiotic, was, however, originally discounted as impractical because of its seeming chemical instability. But by 1940 other British scientists showed that it was reasonably stable when partially purified and dried. Their material, only 50 percent pure, proved to be nontoxic to man and very active against susceptible micro-organisms, including staphylococci. Although effective, penicillin was tedious to purify, and problems of mass production seemed insurmountable when the calamity of war prompted members of the British group to look across the Atlantic for help.

The mass outbreak of typhus during World War I and the loss of countless wounded to secondary bacterial infection, followed in quick succession by the influenza pandemic of 1917–1918. gave urgency to the search for an effective antibacterial agent as we entered World War II. It took the crisis of the Second World War, which harnessed the potential of the American drug industry, until then running a distant second to Europe as a source of new drugs, plus the resources of the Department of Agriculture, to create the antibiotic age. The results were nothing less than spectacular. Success was based upon already developed techniques for large-scale cultivation of micro-organisms, the isolation of Penicillium strains that secreted large quantities of penicillin, and the development of suitable growth media. By September 1943, there was enough of this drug to supply all the Allied forces. This phenomenal accomplishment not only markedly reduced mortality among the wounded but also launched a new and fruitful search for other antibiotics.

After elucidation of the chemical structure of penicillin, in due course natural penicillin was replaced by semisynthetic penicillins, which are comparatively simple to manufacture and which retain the essential molecular configuration of the parent molecule, which is so effective against Gram-positive organisms.

The attempts to prepare semisynthetic penicillins bore an additional fruit. The earliest such attempts, which seemed entirely rational, failed. When the explanation was found, it proved to be an important extension of the antimetabolite principle. Sulfanilamide and p-aminobenzoic acid are essentially planar molecules; thus the analogy suggested by the two-dimensional formulae above is indeed valid. But the unsuccessful semisynthetic penicillins, which appeared to be reasonable analogs of natural penicillin—as these structures are conventionally represented on paper— differed significantly when three-dimensional models, based on x-ray evidence, were constructed. Since then, chemists engaged in the synthesis of new drugs have been acutely aware of the fact that, to be effective, the drug must attach properly to the surface of the enzyme or membrane to be affected, and this must be a property of its three-dimensional conformation.

Extensive screening of soil samples, largely by drug manufacturers, then led to the discovery of an ever-increasing family of antibiotic agents, among them streptomycin, chloromycetin, aureomycin, and terramycin. Although there is as yet no universally effective agent, one or another of these drugs can mitigate virtually all known infections.

Antibiotics have drastically altered the patterns of medical practice. Prior to 1940, thousands of hospital beds were occupied by patients with infectious diseases. Today, in the main, these patients receive a prescription for antibiotics and return home. The morbidity associated with postoperative infections has dropped sharply. And the damaging, once frequent, chain of events that began with a “strep throat” and went on to scarlet fever, rheumatic fever, and serious heart disease has been broken. The search for new and better antibiotics continues in an effort that counts on both rationally exploited chance and accumulated skills and understanding. New antibiotics are still discovered by screening methods in which activity is sought in extracts of thousands of yeasts and fungi and soil samples of unknown microflora from around the globe. Modified, improved semisynthetic compounds then follow as drug designers attempt to deal with the two most critical problems posed by these drugs.

As predicted by scientists familiar with the physiology and genetics of bacteria, as use of antibiotics spread throughout the population, so, unfortunately, did bacteria that are antibiotic-resistant. The antibiotic boom fostered selective processes that bred resistant organisms. Among a normal population of bacteria there are, almost invariably, a few organisms that have spontaneously mutated, the mutation rendering them immune to the bactericidal action of a given antibiotic. As the drug suppresses the growth of sensitive members of the colony, resistant mutants flourish. In some cases, simultaneous use of two antibiotics with differing modi operandi is effective to a limited degree. But the problem is compounded by the fact that resistance, like an infectious disease, is catching. Both by sexual mating and by transduction, a process in which a virus carries a bacterial gene from one cell to another, bacteria can spread their resistance among related strains, and some organisms have been isolated that are resistant to several antibiotics at once. Recent work describing transduction may open the way to “outwitting” this threatening phenomenon, as should continuing improvement of semisynthetic antibiotics that are of greater potency and specificity than natural antibiotics but that are insensitive to the enzymes that destroy the latter.

The spectacular success of these antibiotics gave sharp stimulus to inquiry into their mode of action, an inquiry that continues with increasing intensity. In a few instances, partial answers are already available. Thus, penicillin selectively inhibits one specific enzymatic step in the complex process whereby the cell walls of Gram-positive bacteria are fabricated. Each such wall is a single “bag-shaped” macromolecule built of 10 different kinds of subunits. As the cell grows, or divides, linkages must be broken and additional subunits inserted. Interruption of this process leaves the cell without a casing and, hence, renders it susceptible to damage by diverse physical or chemical changes in its environment. Since mammalian cells employ no such casing, they are unaffected by penicillin. Actinomycin D, which has found only limited use as an antibiotic, operates by interference with the mechanism by which RNA is made on the surface of DNA. Because it affects mammalian cells in the same way, it has found little clinical use as an antibiotic. Streptomycin in some manner so affects the ribosomes of Gram-negative bacteria that they make mistakes in translating RNA into protein, and hence make useless, nonfunctional proteins. As this field progresses—as the secrets of naturally occurring antibiotics are revealed— it should be possible to improve on antibiotics, permitting synthesis of chemical entities that are lethal for invading organisms yet relatively innocuous for man. In each case, the new drug must be so constructed as to fit, sterically, onto an enzyme or a membrane surface in such fashion that it will seriously limit normal function, presumably by extension of the antimetabolite principle.

A more sophisticated understanding of the operation of the pathways by which products are synthesized in the body has offered a new approach to drug design. Early attempts to block the synthesis of a given product, e.g., cholesterol, sought to inhibit an enzyme known to be vital to its biosynthesis. Research generally was directed at finding a drug that mimicked the substrate with which a specific enzyme reacted, as noted earlier. However, a new avenue of pursuit was opened by the understanding that the “committed step” in most synthetic metabolic pathways (pathways that involve a series of consecutive reactions) is subject to allosteric feedback inhibition by the final product, which bears little resemblance to the substrate of the enzyme responsible for the committed step. It is clear that ingestion of cholesterol drastically inhibits its own biosynthesis. Patently, a foreign molecule that, in low concentration, could accomplish the same event might serve as a potent drug for prevention of atherosclerosis, and a series of other such possibilities is also under active investigation. But until the principle of allosteric feedback inhibition had been revealed in studies of bacterial metabolism, this approach could not have been conceived.

There is good reason to expect a considerable increase in the sophistication of drug synthesis in the near future. In addition to the factors considered above, it is evident that many drugs—e.g., morphine and digitalis— work by attachment to specific loci on cell membranes or intracellular membranous structures. Partial understanding of how a drug interacts with a cell membrane at the molecular level has only evolved in recent years. As this field matures—as the structures of membranes are revealed—it may well become possible to alter them usefully in specific states. Quantitative information about the biochemical events in metabolic disease is badly needed, permitting construction of mathematical models of metabolic events in a form manageable in a computer. Such information can be applied in testing new drugs for a given disorder and in determining suitable dosage regimens. For years, the interrelationships between levels of blood glucose and secretion of insulin after the administration of sugar to normal volunteers and to diabetics have been crudely understood. More recently, a carefully constructed mathematical model describes the effect of administered insulin on the uptake of glucose by the tissues, with resultant changes in blood-glucose levels and in the release of insulin from the pancreas. Use of this model permits more nearly normal regulation of the blood-sugar levels of diabetics. The benefits to man to be derived from this advance are not yet certain, but the potential is huge. The insulin regimens available since 1920 have sufficed to maintain the lives of hundreds of thousands of diabetics. In time, however, they progress to a series of highly undesirable sequelae—cataract, peripheral vascular disease, hypertension, atherosclerosis, and a disease of the lining of the minute filters of the kidneys. A generation will be required to establish whether the dosage schedules suggested by the new mathematical model, which, far more than in the past, mimics the release of pancreatic insulin by normal individuals, will also prevent the physical deterioration that is characteristic of diabetics treated with insulin for the last half century.

As understanding of disease has dramatically increased, so have demands for better comprehension of what disease is on the molecular level. Simultaneously, the development of a new drug has become a considerably more complex operation due to the effort to meet increased requirements for specific details about mode of action, specificity of action, safety, and effectiveness in man. From the time a scientist arrives at an idea of the pharmacological potential of a new compound to the time that compound actually reaches the market—a period of five to ten years—a pharmaceutical house must invest between $5 million and $10 million. Yet, this is our ultimate hope for useful new drugs, and increasingly such developments must rest on sound fundamental studies.

VIRAL DISEASES

In contrast to the great success of antibiotic therapy for bacterial infections, only trivial progress has been achieved in coping with viral diseases. A virus consists of a relatively small amount of genetic information, as either DNA or RNA, with a protein coat. This coat is shed as the nucleic acid enters the cell, where it usurps the normal genetic apparatus, shutting off normal production of cellular RNA and proteins so as to turn out many copies of the virus itself. Patently, any drug or procedure calculated to interfere with this process must also similarly interfere with normal operation of the genetic apparatus. Although this is probably tolerable for brief periods in a tissue such as muscle, it could be highly injurious to such rapidly dividing tissue as that of the bone marrow or the intestinal tract. Clearly, drugs intended to serve these ends must possess a very high degree of specificity and, despite much work, only a few useful leads are available. One noteworthy example is the treatment of viral eye infections, e.g., the herpesvirus, with a halogenated pyrimidine compound, 5-iododeoxyuridine. Although quite toxic systemically, it can be safely applied as eye drops. In the eye this compound is incorporated into the new viral nucleic acid, which then, as if mutated, directs the synthesis of inappropriate proteins, and the infection cannot sustain itself.

A recent finding of considerable promise is that an antibacterial antibiotic, rifampicin (rifantin), also has very significant antiviral potency. Its mechanism of action is highly interesting; for unknown reasons, in the presence of this compound, the coat proteins of several viruses cannot assemble on the viral nucleic acid surface. Hence, although both nucleic acid and coat proteins are made in the infected cell, the full virus cannot be assembled and fails to leave the cell in which its components were synthesized, and thus the infection is terminated. Since there is no analogous assemblage in the metabolism of mammalian cells, the antibiotic can be used in animals, in adequate dosage, as an antiviral agent without concern that it will interfere with any vital process in the host animal cells.

For the present, the major defense against virus infection must remain man's own principal defense mechanism, the immune system. The efficacy of this system was long evident in the list of diseases that strike but once in a lifetime, e.g., smallpox, measles, mumps. In each case, the “antigen,” the foreign material that is “recognized” as foreign and that both elicits formation of antibodies and combines with them, is the viral protein coat. Effective defense is possible either by deliberate immunization in advance, or by enhancing the immune response early in natural infection. Deliberate immunization has long been practiced, as in smallpox vaccination, while enhancement of the immune response has, until recently, consisted largely of administration of antibodies from someone who has already had the disease, as in administration of pooled γ-globulin to prevent a suspected case of measles.

Understanding of the nature and behavior of viruses, coupled with methods for culturing them, lay behind the development of the polio vaccine. As recently as 1954, this crippling disease struck 20,000 Americans annually. Eleven years later, only 61 cases were reported in the United States, the dramatic achievement of a mass-immunization campaign. Although the general principles of immunization had been known since Jenner introduced smallpox vaccine, much fundamental knowledge had to be acquired before it could be applied with impunity to the polio virus. It was first necessary to develop a cell system—monkey tissues grown in culture—in which polio viruses could be grown. Initially, viruses grown in this way were chemically inactivated and then administered. The subsequent perfection of live polio vaccines depended upon an independent line of research and the discovery of three mutant forms of the virus that could no longer cause disease but retained their immunizing effect.

A development of molecular biology that may yet offer large dividends is the recently acquired knowledge of a material called “interferon.” This is a protein, perhaps an enzyme, that is produced in small amount by animal cells infected with a virus. In sufficient quantity it increases remarkably the efficacy of the immune response. Until techniques become available for its large-scale production, the best hope has appeared to be stimulation of the mechanism by which one's own cells engage in interferon synthesis. The primary trigger seemed to be the viral nucleic acid. Following this clue, it was found that synthetic double-stranded RNA (a simple polymer devoid of meaningful genetic information) is at least as efficient a stimulus as viral nucleic acid. When given early in an infection—e.g., mice given sufficient virus of hoof-and-mouth disease to assure 100 percent lethality— such material has offered complete protection, not only sparing lives but preventing the disease. This may yet prove to be the basis of a truly useful clinical approach to viral infection with the happy property of being generally useful without regard to the specific virus in question in any given patient.

CANCER THERAPY

Insights into the nature of DNA, its biosynthetic processes, and its role in cell growth and development have had wide application in recent cancer research. Coupled with recognition of the antimetabolite principle, these insights stand behind the development of a series of anticancer drugs that are able to check the growth of tumor cells, prolonging the lives of some patients by several years.

Cancer, second only to heart disease in the mortality tables, is not one but many diseases. Slow-growing solid tumors, such as lung cancer, are extremely difficult to treat unless the tumor is localized so that it can be removed by surgery or destroyed by irradiation. Significant progress has been made in treating by chemotherapy fast-growing tumors such as leukemia or other blood or lymph cancers. Cancer of both types is characterized by abnormal, uncontrolled growth of cells. Successful therapy depends upon an understanding of the metabolism and synthetic activities of those cells and rests on the principle of attacking them when they are in a vulnerable state.

The process of cell replication occurs in four stages: two pauses or resting states, a period of DNA synthesis, and one of mitosis and cell division. Different chemical agents selectively inhibit cell metabolism at different stages in this cycle and, because the cancer cells in an individual are not all synchronized—that is, they are not all in the same phase at the same time— judicious use of a combination of antimetabolites is necessary to destroy the maximum number of tumor cells.

Folic acid is used by man as a coenzyme in the process of synthesis of DNA precursors. Therefore, it was reasoned, an antimetabolite that could disrupt this sequence would inhibit the growth of tumor cells in the DNA-synthetic phase. Of a series of structural analogs that were tested, one called methotrexate (amethopterin) is clinically useful. Its drawback is its lack of specificity; it acts against all cells in the DNA-synthetic phase, whether they are cancerous or not. The turnover of normal cells, however, is distinctly less than that of rapidly dividing cancer cells; in weighing risk versus benefit, it was concluded that the toxic effects of methotrexate are less than its benefits, particularly in the treatment of leukemia.

Another agent in the arsenal of anticancer agents is actinomycin, originally found as an antibiotic, which checks-cell growth by limiting RNA synthesis on DNA. When used against choriocarcinoma, an all too frequently fatal cancer of young women of childbearing age, it effects a 50 percent cure rate (remission of symptoms for five years). In combination with methotrexate, cures are achieved in close to 80 percent of cases. The same combination effects a 70 percent cure rate in Wilm's tumor, a kidney cancer, and a 25 percent cure rate in cases of Burkitt's lymphoma, a malignancy of the lymph glands first identified in children in Central Africa but now known to be widespread. Patently, without knowledge of the mode of action of actinomycin as an antibiotic, there could have been no reason to consider it as a potential anticancer agent.

Progressively more complete knowledge of DNA and RNA metabolism has opened other encouraging new avenues of cancer therapy. One clue came from the observation that rat tumors metabolize excess quantities of the pyrimidine uracil in the synthesis of RNA. Laboratory production of a series of uracil analogs resulted in two compounds that have proved valuable against leukemia cells: 5-fluorouracil and 5-fluorouridine. In addition to their considerable antileukemia action, these agents are effective in about 20 percent of cases of cancer of the colon.

Another drug, cytosine arabinoside, induces remissions in almost 40 percent of leukemia cases and hence is the most successful antileukemic agent yet assayed. Recently licensed by the Food and Drug Administration, this drug was developed after zoologists discovered that a species of sponge contains a class of nucleosides (subunits of RNA) that contain the 5-carbon sugar, arabinose, instead of the normal sugar, ribose. This structural analogy suggested the desirability of testing cytosine arabinoside in an anticancer screen. Until recently, the supply was limited to the very small amounts available from sponges. For several years, no enzymatic or chemical synthesis proved useful. This bottleneck was broken by a group of organic chemists studying chemical events under what are presumed to be the circumstances prevalent on earth when biological macromolecules first appeared, who found that under such circumstances cytosine arabinoside is readily formed. Thus, thanks to a zoologist interested in the biochemistry of sponges, an organic chemist interested in the origin of life, and biochemists curious about the metabolism of this unusual compound, the most useful of all antileukemic drugs tested to date was made available. How long would one have had to await this achievement if only “targeted” or “directed” research were supported?

One more drug, of limited utility in the treatment of leukemia, affords an excellent illustration of the manner in which fundamental understanding leads to practical application. A continuing theme in cancer research has been the thought that a somatic mutation underlies the malignant transformation. If such a mutation led to a metabolic or nutritional difference between normal and neoplastic cells, one might be enabled to utilize that difference in the design of a therapeutic approach. This has been realized in one instance. Of the 20 amino acids found in proteins, 10 cannot be synthesized by man, and hence are nutritionally essential. The other 10 can be synthesized by most human cells, but some cells rely on receipt of such amino acids in the blood after they have been synthesized by the liver. Asparagine is one such amino acid. All cells made in bone marrow are normally capable of synthesis of this amino acid, but screening of leukemic cells revealed that the cells of some patients are incapable of such synthesis and are dependent upon blood plasma for a supply of asparagine. Several micro-organisms make an enzyme, asparaginase, that hydrolyzes asparagine. This enzyme has been highly purified and injected into such patients; their leukemic cells, starved for asparagine, then succumb. The consequence has been a gratifying, sustained remission of symptoms in this small population of patients.

Today, carefully controlled combination drug therapy offers to leukemia victims a survival time of two to five years, whereas only a few years ago, they would have died in a few months. True, permanent cures must await a form of therapy addressed to the not-yet-comprehended underlying cause of these disorders.

Comprehension of the intricacies of nucleic metabolism and of specific metabolic inhibitors of various kinds have applications in other areas of medicine as well. Seldom is an advance confined to a single field. In psoriasis, a disease characterized by excessive growth of portions of the skin, methotrexate, particularly in combination with 6-azauridine, an inhibitor of purine metabolism, brings the disfiguring disease under control, though it is not a lasting cure. In organ transplantation and immunological research, as we shall see, drugs originally developed in anticancer programs have played a primary role in scientific progress by serving to suppress the immune system, the essential step in preventing the rejection of a foreign organ. Yet another drug, 5-iododeoxyuridine, originally synthesized, tested, and discarded as an anticancer agent, as we have seen, turned out to be highly effective in curing herpes keratitis, a virus infection of the eye, thereby preventing what was previously a major cause of blindness in the United States. This advantageous action of the drug has encouraged trials of its effectiveness in obliterating other viral infections, including meningitis and smallpox.

The major question before all those concerned with cancer therapy is the underlying nature of the neoplastic transformation of previously normal cells. It has long been known that many physical agents—e.g., chronic mechanical irritation, carcinogenic hydrocarbons, various dyes—predispose to such transformation. But their role remained unclear. Half a century ago it was shown that papillomas (warts) on rabbit skin contained a virus that, when administered to another rabbit, resulted in formation of more virus-containing papillomas. Other examples followed, perhaps most notably avian leukosis, a disease analogous to but not identical with human leukemias, in which neoplasia followed viral infection. The most dramatic stimulus to this general theorem was given by the demonstration that a remarkable variety of mouse tumors are all consequences of infection by one agent, the polyoma virus. In consequence, an intensive search is in progress for analogous carcinogenic viruses in man. The clearest success to date is the positive identification of a virus in the etiology of Burkitt's lymphoma. But virus-like particles have also been found in the cells of a wide variety of other malignant and nonmalignant tumors; it remains to show their causality.

The viral theory of cancer would seem less plausible were it not for a readily available model in bacterial life. Bacteria are subject to infection by their own specific viruses, bacteriophages. Some of these, the “temperate” phages, enter a cell and disappear, their nucleic acid seemingly becoming an integral portion of the bacterial genome, reproduced only when the entire genome is doubled prior to cell division. However, a sudden change in the environment can result in rapid multiplication of only the viral nucleic acid in the cell genome, with formation of a multitude of virus particles and rupture of the host cell. By analogy, then, carcinogenic viruses could be carried in the genomes of mammalian cells and yet be invisible and of no consequence until some change—e.g., cigarette smoking— accumulated a sufficient challenge to produce specific virus duplication and carcinogenic transformation. The nature of this process is discussed in Chapter 1 .

Finally, it is apparent that this generalization, if valid, has only slight impact on the strategy of anticancer programs. Whether it be the nucleic acid of the host cell or of the virus, all available chemotherapeutic approaches, like x irradiation, must affect the biosynthesis of this component of the system. If the generalization proves valid, the design of anticancer drugs will be more clearly delineated in the future and will become decidedly less empirical.

A significant bonus from cancer research has been the development of a drug for the treatment of gout. Originally synthesized as a potential anticancer agent, in the last few years allopurinol has become the treatment of choice for gout, a disease marked by unusually severe, acute arthritis and, in many patients, by the presence of deposits of chalk-like material that lead to grotesque deformities and serious crippling. Familial in distribution, gout afflicts about 275 of every 100,000 persons in the United States. Allopurinol is effective in a majority of gouty patients, preventing crippling and alleviating pain. It has also become standard therapy in the treatment of patients who form uric acid stones, whether or not they have gout.

In the course of essentially negative experimental trials with allopurinol in cancer victims, it was observed that, during treatment with this drug, patients excreted unusually small amounts of uric acid. That the measurement was made at all derived from the fact that allopurinol was synthesized as an antimetabolite of the purines required for synthesis of RNA and DNA; in normal and gouty individuals, uric acid is the ultimate end product of purine metabolism.

This observation prompted what then proved to be highly successful trials of the agent in patients with gout, a disease in which uric acid deposits accumulate in the joints. Indeed, as long ago as 1850, gouty patients were discovered to have elevated levels of uric acid in the blood.

Approximately two thirds of the uric acid formed each day is excreted through the kidney, and one third by way of the gastrointestinal tract. Because it is so sparingly soluble, it tends to form crystals when its level is elevated in the blood or urine. Allopurinol is structurally similar to hypoxanthine, one of the purines formed by degradation of the nucleic acids and the precursor of uric acid. Because of this structural similarity to hypoxanthine, allopurinol can attach to xanthine oxidase, the enzyme that catalyzes formation of uric acid and can inhibit its normal activity. In consequence, daily formation of uric acid is much reduced, while the hypoxanthine is disposed of by an alternative process, viz., reutilization for nucleic acid synthesis.

A by-product of this work with allopurinol has been elucidation of the genetic basis of a rare form of gout observed in children who also exhibit cerebral palsy, mental deficiency, and self-destructive biting. In these children, while allopurinol effectively inhibits xanthine oxidase, total purine excretion is not reduced as in other gouty individuals. This suggested that hypoxanthine could not be reutilized for nucleic acid synthesis in these children—a postulate that proved to be correct. Thus, the precise metabolic defect in this form of gout, transmitted as a genetic recessive trait by a gene located on the X chromosome, was identified. It may be hoped that such understanding may one day lead to rational therapy. For now, it must suffice to incorporate knowledge of this dreadful disease into sophisticated genetic counseling.

We cannot refrain from an additional note. In all mammals but the primates, uric acid is subject to a further metabolic degradation that leads to highly soluble products. Hence, gout is a disease that can occur only in man and the other primates. But loss of uricase (the uric acid-destroying enzyme) is the only specific biological alteration one can temporally associate with the evolutionary appearance of the primates, and one cannot help but wonder whether the presence of uric acid in the blood is in some manner related to the subsequent rapid evolutionary development of the brain.

GENETIC DISEASES

The first scientist to document the fact that some diseases tend to run in families was A.E.Garrod, physician to the British royal family. In 1908, not long after the resurrection of Mendel's work, Garrod published a remarkable treatise entitled “Inborn Errors of Metabolism,” at a time when almost nothing was known about metabolism. He listed six inborn errors that are transmitted as recessive Mendelian traits. Now, several hundred such genetically transmitted errors have been identified; in many cases ( Table 2 ) the specific missing,enzyme or other protein is known; in other cases ( Table 3 ) it has not yet been identified. It is to be emphasized that, with few exceptions, these genetically transmitted abnormalities are detected because they do, in fact, occasion disease. This comes about, generally, in one of three ways:

Some Hereditary Disorders in Man in Which the Specific Lacking or Modified Enzyme or Protein Has Been Identified.

Some Hereditary Disorders in Which the Affected Protein Has Not Been Identified.

Because of the blocked pathway, a desirable end product is lacking, e.g., in albinism, lack of one of the enzymes responsible for metabolism of the amino acid, tyrosine, renders synthesis of the pigment melanin impossible.

Accumulation of an intermediate that normally is further metabolized may precipitate the difficulty, e.g., the arthritis of alkaptonuric individuals in whom a block in tyrosine metabolism is responsible for accumulation of homogentisic acid.

The blocked pathway may result in diversion of a normal intermediate into an alternative but normally little-used metabolic channel, forming intermediates that themselves cause difficulty, e.g., mental deficiency caused by accumulation of phenylpyruvic acid in phenylketonuria.

In the main, type (1) is predominant, since it also includes the host of situations in which the genetic defect results in a great variety of structural and functional failures. It will be clear that such diseases are the consequence of genetic alteration of important but not vital processes. Undoubtedly genetic alteration of vital processes exists, but is expressed not as defined disease but as complete lethality with failure of the fertilized egg to develop. With few exceptions, all these diseases reflect the presence of the mutant gene in the chromosomes of both parents; hence there is the great potential of genetic counseling in the future to limit such diseases. Finally, we must note again that, without the huge advances in fundamental understanding in the last few decades, it would have been impossible to detect and define this list of defects in man's own essential biology or to arm genetic counselors in the future.

Examination of individuals with inborn errors has contributed significantly to understanding of normal metabolism. The accumulation of a compound not normally observed indicates that it must be an intermediate in some metabolic pathway. Such information has contributed significantly to construction of “metabolic maps” of the multitude of synthetic and degradative chemical reactions that constitute the activities of normal cells. (See Figure 3 , page 38.)

Moreover, in a few instances therapeutic regimens have been developed that markedly mitigate the genetic disorder. Phenylketonuric infants may be detected by a simple test applied to soiled diapers. When placed on diets very low in the essential amino acid phenylalanine, they grow to maturity with essentially normal mental capacity—at least sufficient to obviate the necessity for institutionalization. Galactosemic infants also are now readily detected. A feeding formula containing cane sugar rather than milk sugar prevents the cataracts and bone malformation caused by this disease. Both these procedures get around the genetic disorder by avoiding the problem—eliminating from the diet the material the child is genetically unable to metabolize. But this approach is open in only a few such diseases.

An alternative plan is to replace some of the defective cells of the affected individual with normal cells from some donor. For more than a year and a half, a boy with agammaglobulinemia—a total lack of immune competence—and one with the Wiskott-Aldrich syndrome—a partial immune deficiency—have survived with immunologically competent marrow cells grafted from genetically related siblings. In the United States and abroad, a long-standing embargo on marrow grafting has been lifted because new understanding of the immune mechanism, advances in tissue typing, and methods of controlling immune responses through immunosuppressive drugs have markedly raised the level of knowledge.

In theory, a similar approach might be useful for sickle cell anemia, for example, or for the nongenetic aplastic anemia. However, the massive scale of marrow transplantation then required renders such plans rather unlikely.

The final alternative is repair of the genetic defect itself, viz., introduction of the normal gene into the body cells of affected individuals, an approach that has been called “genetic engineering.” To date, this has not been tried. The proposal is to learn how to transduce the appropriate gene with an innocuous virus—analogous to transduction of antibiotic resistance in bacteria. It is impossible to assay the chances of success in this effort, which will be long and difficult. But there are, at least, no patent theoretical obstacles to success, and mankind would be immensely rewarded.

In this regard, it may be noted that sophisticated knowledge of enzyme systems and microtechniques for identifying them while the fetus is in utero are enabling geneticists to identify an increasing number of metabolic disorders in infants during the first trimester of pregnancy. Most recently, it has become possible to detect Tay-Sachs disease, a fatal neurological disorder resulting from impaired lipid metabolism, in utero . Such techniques offer the parents the option of terminating pregnancy in such cases but raise ethical questions outside the scope of this technical summary.

THE IMMUNE SYSTEM

Mechanisms for resisting infection began evolving in early biological time. Immunity is a highly specific condition in which, having produced antibodies to the toxins produced by bacteria or to the exterior of bacteria and viruses, animals are not adversely affected by their invasion.

The system responsible for antibody formation occupies the current scientific limelight because, if it could be understood and controlled, the possibility of victory over cancer and infectious diseases would be markedly enhanced while one of the major stumbling blocks to organ transplantation would be overcome, and because, intrinsically, it is a fascinating process. An antigen must simply be a foreign molecule of sufficient size to trigger the formation of antibodies. To this day, it remains unclear how a given antigen initiates the process of formation of antibodies that specifically combine only with molecules identical with the initiating antigen.

The first time the body confronts an antigen, it produces a small amount of antibody that slowly disappears from the blood. The response may involve only a few antibody-making cells, but it paves the way for a significantly more powerful response if the same antigen is introduced a month or more later. The immune system, in short, “remembers” the foreign molecules it has encountered before and is prepared to defend itself against them, responding with 50 to 100 times the vigor exhibited during the first encounter. This biological memory is specific, greatly fortifying resistance to a second attack of disease. Infections that come and go suddenly are those in which the attack is successfully thwarted by antibodies. Chronic infections are those in which specific resistance fails.

One of the principal questions before immunologists is the nature of this sophisticated memory. Biochemically, in what kind of compound or mechanism is it stored? Antibodies and antigens fit together like a hand and a tightly fitting glove. Is there, perhaps, a biochemical library in which the shapes of previously encountered antigens are shelved? If so, where? Current hypotheses suggest that storage must be in a protein, perhaps in a variety of antibody protein that may be attached to the surface of a cell, such as a lymphocyte coursing through the blood or a macrophage or a plasma cell precursor in the bone marrow, spleen, or thymus gland. A recent discovery of great importance indicates that antibody formation begins by cooperation between two families of cells—scavenger cells called macrophages, and antibody-synthesizing cells. The macrophage engulfs the antigen, perhaps changing it into a different form, which is a highly active stimulus to antibody formation by plasma cells in lymph nodes and bone marrow. The extent to which this process occurs is dictated by hormones elaborated by the thymus gland, but the exact role of this gland remains obscure.

Particularly intriguing is the mechanism whereby the antigen, or a derivative generated in a macrophage, causes the formation of the highly specific antibody. Antibodies are large protein molecules constructed, as usual, of amino acids, according to the plan shown in Figure 31 . Each such molecule has two combining sites for antigen. Much of the molecule is invariable among all antibodies, while a significant fraction, in two different sections of the molecule, shows variation in amino acid sequence, depending upon the initiating antigen. The problem, then, is whether there are already genes for all possible antigens, with a given antigen serving somehow as a derepressor for that gene which corresponds to the antibody, which combines with itself, or whether, in some manner, there is a set of plastic genes whose expression is altered by presence of the antigen. These two hypotheses seem almost equally unreasonable, and the true mechanism may well differ from either. Until such understanding is gained, knowledge, and hence control, of the immune system must remain essentially empirical.

Schematic structure of plasma immunoglobin. The structure given is that of the major antibody protein of the class IgG. L = light chains; H = heavy chains; CHO = carbohydrate unit. The variable and constant portions of the chains, with respect to amino (more...)

Antibody function, which may take several forms, is only partially understood. The simplest of its activities is to neutralize, by binding at its active site, a toxic molecule, thus preventing its toxicity until it can be destroyed by scavenger cells. With viruses, interaction with the protein coat of the virus may suffice to prevent its penetration into a susceptible cell, and hence account for the usual immunity produced by viral infections and by vaccines. In a more complicated maneuver, antibody may react with the surface molecules of invading cells—e.g., bacteria. Cellular destruction then requires the operation of “complement.” The latter is a group of substances in normal serum that becomes functional only after antibody-antigen interactions take place. Apparently, in a group of hydrolytic enzymes, each activates the next like a row of falling dominoes, the final activated member being the enzyme that attacks and destroys the cell. It is possible that complement, or a deficiency of its naturally occurring inhibitors, plays a role in the development of some autoimmune diseases—instances in which a person makes antibodies to his own tissue, with very serious consequences.

Aberrant functioning of immune mechanisms is associated with a number of important chronic disorders. Common allergies, including hay fever and hypersensitivity to some protein in shellfish, are among these. So are more serious maladies, including an inability to make antibody or the destructive process of making antibodies against oneself. Studies of children with the former disorder show it to be inherited as a recessive trait; the consequence is a continuing series of infections, inevitably ending in death. In contrast are the autoimmune diseases. Acute and chronic kidney disease develops in persons who make antibodies against their own kidneys. Rheumatic fever and damaged heart valves appear in patients whose antibodies fight their own myocardial muscle fibers. Hemolytic anemia can result from antibodies against red blood cells. Multiple sclerosis may well have a related etiology. To date, this understanding has done little to assist in the management of these disorders, but it is the essential first step.

TISSUE TRANSPLANTATION

As was brought to public attention so dramatically in recent attempts at cardiac transplantation, management of the immune system is a key factor in the success or failure of homografts. The problem is still but partially solved, while investigators search for ideal immunosuppressive drugs and regimens for their use. (Too little does not work; too much so paralyzes the immune system that the patient is exposed to repeated infections.) Currently, the search is for means to induce specific tolerance, that is, to induce the immune system specifically to accept a transplanted organ from a given donor while retaining its normal vigor against infection.

When an organ, e.g., a kidney, from a random donor is transplanted, it serves as a source of antigens. The antibodies produced in response can attach to a variety of sites in the transplanted organ and effectively destroy it. Moreover, the transplant may bring with it immunologically competent cells that make antibodies against the host, damaging diverse normal tissues. In the earliest such studies it was shown that transplants involving identical twins posed no such problems. The question, then, is whether a vast number of operative antigens is involved or a lesser, perhaps manageable, number. Although the chemical nature of the antigens remains largely unknown, “typing” procedures have been developed that indicate the presence of perhaps 30 tissue antigens—procedures analogous to typing procedures for classical blood transfusion. Accordingly, it has now become possible to type prospective donors and recipients, thereby permitting identification of suitable donors who are not necessarily identical twins. This is a momentous achievement that, already in use, should go far toward reducing the seriousness of management of the immune system after such procedures, but it has by no means yet obviated this problem.

At the same time, one may well ask, “What purpose, if any, is served by the mechanisms involved in these rejection reactions? Why should cells from one human being be rejected by another?” There is no obvious evolutionary explanation. Since transplantation is entirely man-made, there is no known selective mechanism that would account for one man's biochemical refusal to tolerate the tissues of another. One hypothesis under consideration is that the mechanism evolved and has been maintained to eliminate mutant cells not under normal growth controls, viz., cancer. Indeed, there is evidence to support this view; if true, it suggests that the neoplastic transformation of normal cells may be a frequent event, but that the normal immune system quickly destroys them. Established cancer, then, would be the consequence of failure of the rejection reaction—a distinct possibility.

CARDIAC DISORDERS

Heart diseases take the lives of more than 700,000 Americans annually and disable millions more. Acquired and congenital anomalies need surgical repair. Malfunctioning valves need replacement. Hearts too weak or diseased to beat regularly require regulation or stimulation. And some hearts are beyond repair. These needs have motivated cardiac research for decades. Some have been met; others may be met before long.

Although heart transplantation is an experimental and controversial measure, heart surgery includes a variety of well-established procedures that have saved thousands of lives. Pacemakers save many more, as do drugs that control irregular heartbeats. For these achievements we are indebted to the physiologists who have explored the workings of the heart, to the engineers who designed the heart—lung machine and the miniaturized transistors that power pacemakers, and to pharmacologists for their fundamental research into the chemistry of a heartbeat.

The primary problem of cardiac physiology is accurate estimation of blood flow through the heart. Studies to overcome this problem, begun in the 1920's, and continued ever since, have been richly rewarded. First came procedures whereby, from the behavior of an injected pulse of an indicator dye, one could calculate blood flow. Twenty years later, it was shown that thin, radiopaque catheters could be introduced into the heart chambers via peripheral blood vessels and carefully positioned visually by fluoroscopy, permitting direct sampling of blood in the cardiac chambers. Before complex heart surgery could be attempted, it was imperative that the surgeon have, in advance, precise information about specific functional and anatomical abnormalities. Catheterization, radiopaque dyes, and angiocardiography (x-ray visualization of the heart and associated vessels as the dye passed through them) provided some of this information. Recently, valuable knowledge has been obtained describing the response of the heart to various types of abnormal mechanical overloads from obstruction and insufficiency of the several heart valves; this is especially useful in selecting candidates for surgery.

In short, a variety of increasingly sophisticated and reliable techniques have been developed over the course of half a century. With them the physician can make a highly precise diagnosis, establish the quantitative as well as the qualitative nature of the problem, and rationally decide upon a therapeutic or surgical course. One of the more remarkable aspects of the surgical technique is the recent capability to literally patch major blood vessels and cardiac valves, thanks to the availability of suitable, nonreactive plastics from the chemical industry.

Pacemakers, first used to control cardiac rates in physiological studies on animals, have been employed in animal and human studies ever since the finding that electrical stimulation by high-voltage direct-current shocks, delivered directly to the heart during episodes of fibrillation, induce the return of properly coordinated rhythms with return of normal cardiac function. In fibrillation, the muscular fibrils of the heart twitch rapidly, independently, and irregularly so that coordinated contraction and pumping cannot occur. During the 1950's cardiologists studying patients suffering Stokes-Adams attacks (syncope—bouts of loss of consciousness due to insufficient blood flow to the brain) developed pacemakers that trigger heartbeats by means of small electrical shocks. The electrodes of these little generators are directly implanted in the patient's heart. This procedure has evolved as the optimal therapy for patients with heart block, prevents Stokes-Adams attacks, and also serves persons in cardiac failure characterized by extremely slow ventricular rates.

Antiarrhythmic drugs have also found a valuable place in the cardiologist's arsenal of weapons against irregular heartbeats. The first clinical trial of such drugs took place in 1912, when the effect of quinine alkaloids was observed. Since then, extensive pharmacological studies have attempted to explain the mechanism of the quinine alkaloids in this regard. (Quinidine from the cinchona plant is the most effective.) Not until 1951 did another antiarrhythmic agent, procaine amide, become available. Like quinidine, it depresses contractility of the heart and similarly affects its electrical activity, decreasing the formation of impulses, slowing conductivity and excitability, and prolonging the lag time between beats. These drugs have a like range of clinical use; both have similar toxic effects; both remain the most frequently used agents to control a wildly beating heart.

For most of this period, the hunt for such drugs was entirely empirical. The failure to produce more effective, more specific, and less toxic drugs to control cardiac rhythm stems from the facts that the underlying mechanisms responsible for many arrythmias were, and are, unknown, and that the pharmacology of the existing drugs is imperfectly understood. Knowledge of the electrical basis for the formation and conduction of impulses within the heart gained impetus when it became possible to record the transmembrane potentials of single cardiac fibers by implanting microelectrodes within cells. By means of this technique and associated studies, it became possible to characterize the ionic basis of cardiac electrical activity, to identify the unique properties of certain specialized cells, and to observe the influence of, for example, quinidine and digitalis on these parameters. Now, from studies of the electricity of the heart and of the ionic processes associated with it, highly detailed, though not yet complete, pictures have been drawn of each of the major clinical types of arrhythmia, a new beginning is under way, and suitable test systems are available for the search for specific antiarrhythmic drugs.

Critical to ultimate management of these disturbances is improved understanding of the underlying electrical activity, which is the result of the operation of the cellular “electrolyte pump.” It must be more than fortuitous that the “cardiac glycosides,” particularly ouabain, which can assist a failing heart are the most effective known inhibitors of the cellular transport system, which, in cardiac muscle as in all other cells, achieves the outward movement of sodium ions and the inward movement of potassium ions using the energy of ATP. The responsible protein is associated with cell membranes; the model proposed in Chapter 1 for transport processes seems an adequate description of its function, viz., binding of 3Na + and 1ATP, a conformational change that permits rotation in the membrane, hydrolysis of the ATP, discharge of the Na + , binding of K + , and rotation to the original position. Control of this basic life function, which is adapted to the special purpose of “electrical” conduction in nerve and muscle fibers, appears central to progress in a variety of cardiac disorders. Parenthetically, one may note that hyperactivity of this system in the various secretory glands is one of the manifestations, now used as a definitive diagnostic sign, of cystic fibrosis. In yet another context, it is the genetically controlled synthesis of this same transport protein in kidney tubules that is regulated by aldosterone, the adrenal hormone that, in excess, causes Cushing's disease and lack of which occasions Addison's disease.

The advent of cardiac surgery (and indeed, of cardiac transplantation) is one of the most dramatic episodes in the history of medicine. Clearly, these heroic procedures could not have been attempted until all the necessary knowledge, skills, materials, and tools were at hand. Illustrative is the instrument that has become the sine qua non of modern heart surgery—the heart-lung machine.

When the heart is opened for repair of a valve or closure of a hole betweenz the two ventricles (pumping chambers), the heart—lung machine is temporarily employed to assume the function of the heart and lungs, to pump blood, supply oxygen, and eliminate carbon dioxide. First used successfully in man in 1953, its origins can be traced through preceding centuries to the 1500's and 1600's, when double-valve, one-way pumps were designed to draw water from deep mines. These, in turn, apparently inspired William Harvey to recognize the true nature of the heart, which he likened to a water pump. In the 1800's, physiologists attempted to duplicate the work of the heart by perfusion of various animal organs such as the liver and kidney, using a pump to better understand the functions of these organs. In time, physiologists tried to add oxygen and remove carbon dioxide from the blood used in perfusions, thus experimenting with crude forerunners of the heart—lung machine. Their glass, rubber, or metal parts, however, severely damaged the delicate red blood cells, a fact of little consequence in short-term experiments on isolated organs but of obvious import for human application. The plastics industry solved this problem by offering virtually inert, smooth plastics with nonwetting surfaces, which minimize damage to the blood cells as they pass through the pump.

Once developed, successful application of the heart-lung machine awaited solution of one other problem. When blood comes into contact with surfaces other than normal blood vessels, it clots. Indeed, this would happen in the blood vessels themselves were they not coated with natural anti-clotting compounds. Among these is heparin, which can be obtained in quantity from beef lungs. Heparin inhibits the clotting mechanisms, permitting blood to course through the tubes and chambers of the machine for hours.

Many refinements in recent years have made the heart-lung machine safer and more readily available. Artificial heart valves and plastic blood vessels, developed in collaboration with engineers, are available to surgeons. Even totally implantable artificial hearts have been tried in man. And long years of animal experimentation, coupled with the availability of immunosuppressive drugs and techniques for determining tissue matching, make human heart transplantation a feasible, though still highly experimental, procedure. Yet the road ahead is long. Oxygenators causing less damage to blood than those currently available are needed if heart-lung bypass is to be applied for long periods of time. Such an instrument is essential to save patients with serious but reversible lung diseases, such as hyaline membrane disease in newborns. The use of artificial pumps either partially or completely to support the circulation of patients during a heart attack is a logical move that has already been attempted, but it is far from routine and demands considerable refinement. Significant progress toward production of totally artificial hearts is thwarted by our inability to produce compact, long-lasting power sources capable of responding to the biochemical signals that control muscle blood flow. But there is reason to hope.

Remarkable as all these accomplishments are, it must not be forgotten that a large fraction of the conditions that impose these requirements for drastic surgery are the consequence of one process, atherosclerosis, the deposition of mushy lipids on the surface and within the walls of the arteries, which then calcify, become brittle, and serve as foci for clot formation and infection. In the long run, it is to be hoped that understanding of this process will permit its prevention, thereby obviating the need for many current surgical and therapeutic procedures. The alternative, more than a thousand cardiac transplants per day in the United States alone, is scarcely an appealing prospect. Meanwhile, the efforts of thousands of scientists have brought surgery to this remarkable peak.

If the physiologist originated the idea of a heart-lung machine, he also has greatly benefited by its sophisticated use in the hands of surgeons and engineers, for today he uses the same instrument as a tool for learning still more about the intricate mechanisms of the heart and lungs. And, eventually, the information he gathers will further enlighten the physicians and surgeons in their battle against disease.

Diuretics A serious, occasionally life-threatening, complication of heart failure, liver and kidney diseases, and hypertension is edema, the excessive accumulation of salt and water in body tissues at large. Today, diuretics, drugs that interfere with the mechanisms by which kidneys retain sodium, and hence chloride and water, control edema rather successfully in most patients. A major class of modern diuretics was made possible by observations during the early history of sulfanilamide. Ironically, no one would have predicted that the background essential to the rational development of diuretics would be supplied by research quite unrelated to the function of the kidney or to the need for such agents.

Early in the clinical use of sulfonamides, it was noted that such patients excreted an alkaline urine and developed a mild acidosis (acidification of blood plasma). Then, biochemists observed that sulfanilamide inhibits the enzyme carbonic anhydrase that catalyzes the simple hydration and dehydration of carbon dioxide, a process necessary to the escape of carbon dioxide from the blood as it travels through the lungs. When carbonic anhydrase was then found to be present in quantity in the kidney, it became apparent that this enzyme plays a role in kidney mechanisms for excretion of acid and that sulfanilamide's inhibitory effect on the kidney enzyme accounted for its effect on urinary secretion, with consequent acidosis. Accumulation of acid is the consequence of excretion of sodium ions. In otherwise normal individuals, e.g., the sulfanilamide-treated patients, this effect is undesirable. But in patients whose kidneys are failing to excrete salt (sodium ions) normally, the same process could be decidedly beneficial. At that point, chemists had a rational test system for fashioning a drug that would be a more effective inhibitor of carbonic anhydrase than sulfanilamide by modifying the structure of sulfanilamide, and designed acetazolamide (Diamox), which, in 1950, became the first useful oral diuretic. Incidentally, it also became a remarkably successful agent for treatment of glaucoma, excessive secretion of fluid into the anterior chamber of the eye, by interfering with the carbonic anhydrase of the overactive secretory cells.

While Diamox was safe, it was not an ideal agent because it could not be used continuously. Five years later, by continuing modification of the basic structure, another diuretic, chlorothiazide (Diuril), was constructed and proved useful not only for treatment of water and salt retention in ambulatory, nonhospitalized patients but also in lowering their blood pressures. In the five-year period following its introduction, prescriptions for diuretics in the United States increased sixfold. But Diuril, too, had limitations, particularly limited ability to cope with massive edema and excessive stimulation of urinary excretion of potassium and sodium. Pharmaceutical chemists then looked to aldosterone, the adrenal hormone that normally occasions retention of sodium and loss of potassium from the body. Several compounds that structurally resemble aldosterone, yet are sufficiently different that they do not possess its pharmacological actions, were synthesized to displace the hormone from sites where it is normally bound in the kidney. By thus occupying the effector sites of the natural hormone, they function as antimetabolites and prevent excessive secretion of potassium.

Meanwhile, another approach resulted in a diuretic of an entirely different class. It had long been known that mercurial compounds are diuretic, but their toxicity precludes their use. These agents were known to work by reacting with sulfhydryl groups of proteins in the lining of the kidney tubules. Accordingly, a compound was sought that also reacts with such groups but lacks the toxicity of mercurials. The result, ethacrynic acid, is so effective that it must be used with great caution. Happily, like Diuril it can be taken orally. With this armamentarium it is now possible to treat successfully virtually all forms of salt retention except for those that reflect primary disease of the kidney itself. Such cases can be managed only by dialysis with an “artificial kidney,” itself the product of two decades of research, entirely dependent upon growing understanding of the role of a normal kidney.

As is so often true in science, new discoveries seldom have only a single application. Investigations of sulfanilamide culminated in establishment of the antimetabolite principle and development of Diamox, and Diamox, in turn, became an important tool for fundamental research. First, it represented the beginning of a rational scientific approach to seeking diuretics by relating chemical structures to kidney mechanisms. Second, it became extremely useful as a device enabling renal physiologists to evaluate the role of carbonic anhydrase in kidney-transport processes. It was of prime importance in elucidating the renal mechanisms of bicarbonate reabsorption and hydrogen secretion. The concepts thus developed were then amply supported by direct renal-micropuncture experiments. This development had an important influence on clinical care of patients because the new understanding of physiology enabled scientists to predict the specific electrolyte losses in the urine produced by various drugs.

Much public concern and attention is directed to the problem of providing the best of medical care to all Americans, a concern we fully share. But the nature of medical care and its relation to research should be clearly understood. The component of medical practice that makes the greatest demands on our resources—measured in the time of physicians, nurses, paramedical personnel, hospital beds, and the ever more complex technology of intensive medical care—is the management of those disorders for which research has, to date, made possible only palliative or physiologically corrective measures, termed by some “half-way medical technologies.” When research has provided a definitive therapeutic or preventive regimen, it is invariably cheaper and simpler than the palliative treatment previously available for the same disease. This is surely true for a wide range of infectious diseases such as lobar pneumonia, poliomyelitis, tuberculosis, bacterial endocarditis, typhus, typhoid fever, and diphtheria, to name but a few. Almost all nutritional diseases—e.g., pellagra, beriberi, rickets, and scurvy—and a variety of other ailments such as pernicious anemia, Addison's disease, goiter, juvenile diabetes, Parkinsonism, and glaucoma fall within this category. Only a few years ago, it was these disorders that dominated the efforts of the health care system. Most remain serious, but they are but a minor aspect of medical practice. The diseases that now overwhelm the health care system are those for which research has not yet provided the understanding required to design truly definitive procedures. It is not lack of physicians, nurses, technicians, or hospitals that limits our capability to manage such problems as most forms of cancer, coronary occlusion, myocardial infarction, stroke, acute rheumatic fever, osteoarthritis, pyelonephritis, bronchial asthma, schizophrenia, muscular dystrophy, cystic fibrosis, and multiple sclerosis; it is lack of understanding sufficient to permit development of a really therapeutic procedure. Biomedical research, which represents only 1.5 percent of total expenditures for health, is, therefore, both the biggest health bargain one can purchase and the only hope for future progress. If this opportunity is neglected or minimized for shortsighted fiscal reasons, then, by the turn of this century, our nation must double the number of physicians, nurses, technicians, hospital beds, and sanitaria and learn to live with the equivalent increment in human suffering. Grim prospect indeed!

Population Control

While biomedical scientists pursue greater sophistication in the understanding and treatment of disease, this attempt must be matched by a concerted effort to solve the crisis being brought on by the continuing increase in human population. No matter what contributions scientific investigation and new technologies make in the coming decades, it is hard to imagine that they will come quickly enough or be sufficient to meet man's needs if his sheer numbers continue to mount unchecked. The problems of population control are both biological and sociological. From studies in reproductive biology must come new and better contraceptive procedures, which must then be put into general use.

The oral contraceptives that became widely available in 1961 are consumed by millions of women the world over; they symbolize society's recognition of the need for birth control. They also illustrate the beneficial results of concentrated, deliberate research. Birth-control pills in current use are usually a combination of the two hormones that regulate the reproductive cycle—a synthetic estrogen and a progestin, a synthetic version of natural progesterone. If taken as prescribed, they appear to be almost invariably effective, although reproductive biologists are not entirely certain why. That these agents strikingly alter the output of the related regulatory pituitary hormones is certain. Beyond that, explanations of their mechanism of action are tentative. They may not actually prevent ovulation each month, yet exert their contraceptive effect nonetheless. The appearance of the endometrium that lines the uterus is somewhat altered in women taking these drugs; perhaps this relates to the failure to conceive. Another possibility is that the progestin in the combination products stimulates the release of cervical secretions so viscous that they effectively entrap spermatozoa. Indeed, there is some evidence that progestin alone is an effective contraceptive, and various experiments with low-dose progestational compounds are under way. Unfortunately, it was one of this class of compounds that was recently shown to induce tumor formation in dogs; hence, the future of this program is uncertain.

The availability of the current pill is the culmination of 70 years of study of the operation of the mammalian reproductive apparatus. Step by tedious step, understanding of the nature and function of the two pituitary hormones—the estrogen of the ovary and the hormone of its corpus luteum —as well as the progesterone of the uterus—was achieved. The accumulated information found its way into pregnancy tests, diagnoses of abnormal pregnancies, and correction of faulty development of secondary sex characteristics. Natural sources of estrogens and progesterones were inadequate; substitutes were synthesized that were more effective than the natural forms and that could be taken by mouth. Detailed studies revealed the precise cellular changes occasioned by each natural and synthetic hormone; slowly, the precise clockwork that governs the menstrual cycle and the stabilization and climax of pregnancy was elucidated.

With such knowledge came successful diagnosis of the cause of a large fraction of all instances of sterility—imbalance of the two pituitary hormones. Therapeutic trials failed until it was realized that only human hormone is effective. This is available in urine, and a modest supply now permits pregnancy for many childless wives. But the supply is limited and one must await precise establishment of the amino acid sequence of this hormone, followed by synthesis using the recently developed methods for polypeptide synthesis, to overcome this shortage.

It was with this slow and difficult accumulation of understanding that the search for a contraceptive pill began, both estrogens and progestins being tested separately before it became clear that a combination might be required. Most important is the realization that, until the whole stage had been set, the final undertaking could not have been possible. There has been no better illustration of the culmination of many years of interaction between clinical observation and clinical and basic research. As use of the pill increased, reports of clotting disorders and breast tumors became more frequent. Even at this writing, the validity of such claims is somewhat uncertain, and the adverse effects of the pill remain to be established with certainty. Assuming the reality of such effects, there remains the societal decision of weighing hazard against benefit—the death rate due to pregnancy versus that associated with the pill and the risk entailed versus the societal imperative that population growth be brought under control. Meanwhile, the search for other, less hazardous but still effective, measures must be prosecuted vigorously.

The search for contraceptive drugs began with animal studies and now returns to the laboratory to create the next generation of pills. In addition to seeking an explanation of the mechanisms of current agents, investigators must explore the phenomenon of conception itself even further. A quite subtle interruption in this delicately balanced sequence of biological events may well prevent conception just as surely as the grosser effects of present agents.

The newly established Center for Population Research at the National Institutes of Health has initiated a program focusing on four targets:

The reproductive physiology of the male, particularly the processes that permit the maturation of sperm cells. Only a mature sperm can penetrate and fertilize an egg. If the biochemical events surrounding this process could be controlled, a new approach to contraception would be available.

The structure and function of the oviduct through which an egg travels from the ovary to the uterus.

The function of the corpus luteum, the yellow body, formed after ovulation, that produces progesterone for the maintenance of pregnancy.

The biology of the fertilized egg cell before and during implantation in the uterine wall.

Prior to the introduction of oral contraceptives, reasonably satisfactory methods of mechanical or physiochemical contraception existed. Human nature limits the success of these methods; all too often they are used improperly or not at all. They are not, however, to be discarded, nor are the increasingly satisfactory intrauterine devices. If population control is to be achieved on an acceptable scale, a variety of contraceptive methods will be required. This will be possible only in the light of additional knowledge.

If indeed a promising lead for the development of a new contraceptive drug does emerge from research, there will remain an extremely lengthy process, prescribed by the Food and Drug Administration (FDA), before it can be brought to market. Such research and development is performed in the laboratories and under the auspices of pharmaceutical companies, which spend collectively, even now, more than half of all funds devoted to research on reproductive physiology, quite apart from the high costs of prolonged toxicity testing and development. Precisely because such a drug would be taken by “normal” women over many years, the FDA procedures are conservative, demanding prolonged test trials to establish safety, side reactions, and so on. At best, there can be no way to shorten the testing trials in women—and the world's population will have increased by at least one billion before widespread, unrestricted use of such a new drug could be considered, even if the structure of the compound were known, its synthesis worked out, and its general biological properties known at this writing. The great expense of the necessary prolonged procedures is a serious deterrent to the undertaking of such activity by the drug manufacturers, who must somehow be assured that they will at least recover their investment. Meanwhile, the needs of humanity are so great that we suggest that the Secretary of Health, Education, and Welfare develop some new set of relationships wherein the government joins with the drug manufacturers in funding such research activities, utilizing to the full the organized multidisciplinary capabilities of these organizations, underwriting their costs, and pooling their competence. Confronted by the crisis of population growth, the government is justified in taking emergency measures.

The Early and Latter Years of Life

Half the individuals born today will die before their seventieth birthdays; yet, for all the hazards that beset man during his middle years, the gravest threat remains with the first year of life. Infant mortality (deaths in the first year of life) has been declining steadily in the last half century as a result of significant advances in infant care, but it is still higher in the United States than in several other countries—22.1 deaths per 1,000 live births in 1967.

Human biological potential is conditioned, in large measure, by the events of prenatal and early postnatal life. The quality of adult life is predetermined by such phenomena as inherited defects, environmental influences, including disease, exposure to radiation or drugs, and the quality of nutrition. The first stages of man's life are the object of growing scientific attention, yet there are few areas in which clinical applications are as severely handicapped by lack of fundamental understanding.

There is, as yet, no precise description in biochemical terms of the mating of sperm and egg. The fetus, in the protective environment of its mother's womb, nourished through the placenta, is particularly susceptible to environmental influences as its cells differentiate and become specialized tissues, and it is subject thereafter to the health of its mother. Diabetes, toxemia of pregnancy, and blood-group incompatibility can threaten its health, and even its survival. Parturition must come neither too early nor too late, and the newborn must then adjust to his world. Whereas a significant fraction of infant mortality may be eliminated by applying available understanding, further progress will be entirely dependent on improved knowledge of the entire process from conception to the early years of life.

No problem appears more urgent than definitive establishment of the consequences in later life of early nutrition. This problem first came to attention with respect to peoples of developing nations as it became evident that the apathy, stunting, susceptibility to infection, lack of energy, and, perhaps, limited intelligence of certain tropical populations were related to their nutritional status, since this characteristic is particularly obvious among those groups in which kwashiorkor (generalized protein deficiency) is rife. Significantly, the data also indicate that there is no genetic basis for this problem. Accordingly, there is urgent need to learn how protein deficiency results in these sequelae, whether there are key amino acids, what level of nutrition is required to prevent the process, etc. Early evidence strongly indicates that the brain of the protein-deficient individual may contain as many as 30 percent fewer than the normal number of neurons (nerve cells). Since the process of neuron generation is completed within the first two years of life, this deficit can never be overcome. Solution of these problems could go a long way toward helping protein-deficient people to help themselves. Equally important is the need to establish the extent to which similar nutritional influences are at work in the United States. Animal studies will continue to be revealing, but safe and sensitive techniques for monitoring the physiological state of the fetus as it develops are sorely required.

To know the mechanisms of genetic and environmental effects and to comprehend the role of nutrition, the influence of hormones in fetal life, and the interactions of tissues, these factors must be measured and charted. Efforts to accomplish this are under way. New methods are now being applied to measurement of maternal excretion of hormones, particularly estriol (an estrogen), and relating it to fetal development, to monitoring of fetal heart rates and correlating these with the fetal condition, and to analysis of fetal blood, even during labor itself, by obtaining microsamples that are examined by new microchemical procedures.

At the opposite end of life's scale, the process of aging is even less well understood. Indeed, it has yet to be described adequately. What processes are responsible for the progressive decline in the structure and function of an adult organism? What aspects of the process are intrinsic to the organism, i.e., the consequence of its initial genetic complement, and what aspects result from environmental assaults? How would we age in the absence of intercurrent trauma or infectious disease? In both young and old organisms, muscles contract, nerves conduct, glands secrete, and so on. The changes occurring in tissues that distinguish youth from age are too subtle to be detected by currently available techniques. How does deterioration in structure and function become incompatible with life? Has anyone ever died of “natural causes”?

One aspect of aging seems incontrovertible. With the passage of time, cells die in certain organs—the brain, the muscles, the lymphatic system— and are not replaced. Is aging merely the consequence of this one-way process? If so, what clockwork fixes the norm for a mouse at one year, for man at three score and ten, for the giant sea tortoise at 500 years, and for the sequoia at several millennia? Can this clockwork be reset?

One prominent theory of aging holds that it reflects a developed instability of the genetic apparatus of individual cells, i.e., that aging occurs because of highly specific deviations within single cells rather than among whole cell populations. Perhaps, for example, in the course of time, subtle errors in the self-duplicating process of DNA accumulate. Perhaps the accuracy of transcription fades, though it does not fail completely. To date it has been possible only to refine these questions, not to subject them to rigorous test, for lack of a reasonably short-lived but acceptable model. Current efforts utilize mammalian cells in tissue culture and such organisms as the thousand-celled rotifer. A suitable test model should have a short life-span and well-established standardized nutritional requirements, should be maintained in freedom from infections and other external insults, and must possess genetic uniformity.

An alternative hypothesis suggests that, whereas cell death and failure of replacement do indeed lie at the heart of the aging process, the reason may not be intrinsic in the cells themselves but may be secondary to changes in their environment. Certainly, with the passage of time, connective tissue becomes tougher, thicker, and less elastic. If such changes also occur on a minute scale at the level of capillaries, this could result in local nutritional failure or intoxication by the products of the cells' own metabolism.

Regrettably, all such studies are in their infancy. Only when they have produced sufficient understanding will it be clear whether man may aspire to a prolonged span of enjoyable, fruitful years.

This brief summary has only touched upon the approaches to biomedical research that may be anticipated in the next decade. Predictions of the future direction of clinical investigation, like those of other human affairs, are hazardous, but the record suggests that the greatest benefit will accrue from the slow accumulation of basic knowledge concerning the nature of normal and pathological physiological and chemical processes. Obviously, one cannot apply knowledge to the prevention and treatment of disease until that knowledge exists.

Biomedical research has come of age. In the intensively managed, highly instrumented clinical research units of our great hospitals, clinical investigation has become a legitimate science. Human biology is being explored with unprecedented vigor and sophistication, and the information net of the biomedical community assures that scientific discovery in all disciplines is readily applied to human disease.

This endeavor, the focal activity of university medical centers, is less than two decades old. How, then, shall one measure its success? Not alone by the large and small insights into the nature of life or the pathogenesis of disease, nor by the pain alleviated or the lives saved. We are all too aware of the woeful limitations of medicine, of the anguish of suffering, tortured humanity, including those who are left behind after death. The true measure of this research enterprise is to be found in the hopeful spirit of the biomedical research community as it faces the future. The increasing wealth of information and insight provided by molecular understanding of normal structure and function and their pathological aberrations render this community confident that it will be armed with ever more powerful tools with which to undertake its noble task.

ON FEEDING MAN

In ten years' time, human beings will eat human beings in Pakistan.

—PRESIDENT MOHAMMED AYUB KHAN, 1964.

If man is to control his own destiny, he must understand his world as profoundly as he must understand himself. Only when there is a balance between the human population and its food supply will the threat of mass starvation be lifted. But calories alone will not suffice; the protein and vitamin content of the food supply must also be adequate to human need. Moreover, a balance in planetary terms could well be misleading. In the long term, each major population group must feed itself.

Accomplishment of these goals is a major challenge to the human race, but it is feasible. Indeed it is in prospect, although that seemed unlikely only a few years ago. Mild optimism in this regard rests on the facts that:

On a worldwide basis, food supply has been increasing faster than has population for several years.

Recently introduced strains of wheat, rice, maize, sorghum, and millet have dramatically increased food production in areas in which food shortage has been traditional.

Population control is gaining worldwide acceptance and its practice is increasing, albeit less rapidly than might be hoped.

A sound scientific basis has been constructed for agricultural practice; its extension, worldwide, coupled with provision of the necessary capital, could undoubtedly assure an adequate food supply for a world population that can limit its numbers to only moderate growth in the future.

Modern agricultural practice is one of the greatest of scientific triumphs. Since the turn of the century, agriculturists have been quick to utilize the most recent applicable understanding of genetics, plant physiology, soil chemistry, and physics. The result, combined with generous use of fertilizer in the developed nations, is that an ever-diminishing fraction of the working population is required to feed the remainder, who enjoy the most diverse and nutritious food supply in history.

Crop Yields

Genetics and agricultural practice.

The primary challenge to the farmer is to achieve the greatest possible yield of his crops. His actual choice of crop rests on market forces—price and regional eating habits—coupled with the suitability of his farm for specific forms of tillage. Thereafter, the result depends upon the genetic strain employed, application of fertilizer, soil and cultivation management, control of pests and weeds, water supply, and harvest. The first, choice of genetic strain, is undoubtedly the most successful of all applications of genetic understanding, and in the United States is the basis of a significant industry. For example, dozens of strains of wheat, tomatoes, and hybrid corn are under cultivation in this country. They have been developed to maximize crop return under diverse local circumstances—mean temperature, temperature maxima and minima, amount of rainfall, soil structure, and resistance to infection by specific viruses and fungi—and also to take advantage of heavy applications of fertilizer. Mutants tested in research stations are selected and improved by commercial breeders, who make stocks available to seedsmen, who in turn make them commercially available. A few examples will suffice.

Photosynthesis is the function of the leafy structure of the plant, and crop yields can be significantly increased by maximizing that fraction of solar energy per acre that is absorbed by the crop leaves. This is achieved in part by the spacing of rows, but a major limitation is imposed by the shading of lower by upper leaves. This problem can be minimized by increasing the verticality of the upper leaves. Strains of all major grains are now being bred to achieve this; already it is clear that substantial gains will thus be realized, particularly in semitropical regions where intense sunlight exceeds the light-absorptive capacity of the upper-leaf canopy.

Selective breeding has also improved the desirable intrinsic properties of many major crops. Tomatoes now under commercial cultivation contain several times the vitamin C concentration of older strains. Sugar beets were made competitive with cane by raising their sugar content from 6 to 18 percent, while, at the same time, new strains of cane were developed that do not flower for several months, thereby doubling their sugar content. Success in the breeding of maize affords examples of the use of genetics and breeding methods in agriculture. Maize, or Indian corn, originated in prehistoric times in the highlands of southern Mexico. It has remained to become the most productive of grains, sometimes referred to as the backbone of American agriculture. At first, it was improved, even by prehistoric man, by field selection of outstanding plants for seed. But early in this century, the possibility of greatly increased productivity by hybridization of inbred lines was realized. Most corn now produced in the United States is grown from hybrids that best fit the many demands of local conditions. When the opportunity is taken to aid corn production in developing countries, field selection of varieties is first resorted to for expediency before undertaking the slower development of hybrids.

Corn has the drawback of being deficient in the content of the nutritionally required amino acids lysine and tryptophan. Fortunately, the corn plant was chosen early for detailed genetic mapping and study of the functioning of inherited characteristics. Among the genes studied were two designated as opaque-2 and floury-2. The action of these genes determines in part the degree to which synthesis of the protein zein in the grain is replaced by glutelin of higher lysine content. Incorporation by breeding methods of one or both of these genes in the chromosomes of desirable varieties and hybrids is now in progress. This promises to alleviate, in part, the protein deficiency of world diet, particularly in some Latin American and African nations.

An improvement in protein quality similar to that realized in corn is now in progress for rice. Rice protein is nutritionally excellent, qualitatively, but the amount of protein per serving is rather limited. The results to date indicate that a gain of more than 25 percent in protein content of the rice grain over that of varieties now in use can be attained. The situation for wheat and sorghum is also promising.

Wheat and rice, like sorghum, corn, and other grains, can be bred as dwarf varieties. The wheat and rice dwarf varieties have short, stout stems, allowing greater numbers of plants per acre and use of fertilizers at the higher rates necessary for attaining high yields. Resistance to some of the prevalent diseases can be incorporated into the dwarf varieties, and the protein content of the grain can be changed. All these endeavors are in progress in the strikingly successful programs of the Rockefeller and Ford Foundations for improvement of agriculture in developing countries.

The soybean, which is valuable as a crop because of its high protein and oil content, presents considerations somewhat different from those pertaining to the grains. Although its use was recorded in Chinese materia medica as early as 2838 BC, it was not used as a crop in the United States until about 1900. The United States is now the leading producer, with an annual crop of about one billion bushels.

The soybean plant was at first poorly adapted to growth in many areas. It was discovered that its flowering and yield depended on the length of the day and consequently varied strongly with latitude. Varieties were therefore bred for restricted latitude regions. A variety suited for culture in Arkansas would be killed in bloom in Iowa, where the season is too advanced for maturing when days become short enough for blooming. This property of the plant is a display of the endogenous biological rhythm that is also important for reproduction of many animal species and is present in man.

The quality of the soybean can be varied by breeding to vary the oil or protein content. The slowly changing economic need for the one or the other allows adequate time for development of appropriate strains. Yields of fields, however, even now are relatively low in terms of maximum known yields; the reasons for this are now being sought, with interest centering on factors controlling the extent of flowering and retention of fruit.

Like animals, higher plants are subject to infection by many micro-organisms—by bacteria, fungi, and viruses. In a field unmanaged by man, an equilibrium is achieved among all these, as well as insects and predators. But man-managed monoculture, with great acreages planted with a single strain of one crop, are far more susceptible to such infections, which are not tolerable in agricultural practice. Moreover, few useful therapeutic measures are either available or desirable in view of the low value of individual plants. Accordingly, the success of monoculture rests on the breeding of resistant strains.

Although, even now, 10 to 15 percent of each major crop is lost to infectious disease, virtually the whole of American agriculture consists of plantings of strains especially bred for resistance to specific pathogens. In this way, the wheat crop was saved from attack by bunt (stinking smut) and rusts. Genetically based resistance to both of these diseases exists and is constantly being exploited. Varieties are bred that have resistance to the dominant strains of rust in a particular region. After a few years, however, mutant strains of the rust fungus develop that are capable of invading the wheat varieties in use. Meanwhile, other wheat varieties selected for resistance to the mutant rust are developed and introduced. There is yet little hope of breaking this cycle of resistant plant, mutant fungus, and back again.

Beans and cotton have been protected, albeit only in part, from fungi and root rot. The sugar-beet industry was almost abandoned because of the huge losses to “curly top” virus until resistant strains were developed. And the oranges of Southern California were almost lost to the virus causing “quick decline,” which was transferred by aphids through the sour-orange rootstocks in common use. Only the last-minute discovery of resistant rootstocks saved this industry. Numerous other instances of the application of genetics to practical agriculture could be described, but these should suffice to indicate the scientific sophistication of these endeavors.

Agricultural Practice

Once a suitable strain of crop plant is available, adapted to local climate, and as resistant as possible to serious disease, successful agriculture then requires an adequate water supply, intelligent management of the soil, and minimization of ravages by pests. The soil is the farmer's principal resource, and its conservation is imperative. Optimal tilth depends upon a suitable combination of sand, silt, and clays maintained in miniature aggregate by the degradation products of plants formed many years before that lead to the formation of humus. The combination should prevent puddling or compacting, permit easy penetration by root hairs, water, and air. Salinity and lack of drainage must be avoided. Only recently has soil received the close attention it warrants so that crop production can be maximized by application of rather precisely formulated fertilizers, addition of nitrogen-fixing bacteria, pesticides, and herbicides. In combination, these have been responsible for the increments in crop yields of recent decades. Moreover, attention must be paid not only to the major minerals— potassium, nitrogen, phosphorus, calcium—but to trace elements as well. The nutrition of citrus trees growing on sandy soils in particular must be watched carefully. In many of the western states particular difficulties are met by assuring adequate iron supply for many crops and taking care with interaction of iron, copper, zinc, and phosphate nutrition. If legumes such as soybeans, alfalfa, or clover are raised, the presence of suitable strains of nitrogen-fixing bacteria—the Rhizobia —is necessary. Few agricultural triumphs exceed the rich reward gained by application of traces of cobalt to Florida grazing ranges. This metal, then found in the grasses, is utilized by rumen bacteria for synthesis of vitamin B 12 . For grazing cattle, rumen bacteria are the only source of this vitamin, which is entirely essential to them as to all animals. The entire Florida cattle industry rests on the scientific detective work that elucidated the basis for the emaciation of Florida cattle in early years and provided this almost absurdly inexpensive solution.

Soils are living microcosms; if permitted to die, their useful rejuvenation is extremely difficult. Below the surface are bacteria, actinomycetes, fungi, and algae in prodigious numbers. An equal living mass of animals—nematodes, mites, springtails, earthworms, potworms, ants, insect larvae, and even the larger burrowing animals—cohabit this domain. Successful agriculture requires continuation of this equilibrium. But it can be seriously altered by monoculture; crop rotation was long ago recognized as a partial answer to this problem, although devised entirely empirically. It is an expensive way to use valuable land and today need be done only for specific reasons. For example, rotation with barley can be used to reduce the population of saprophytic fungi in the soil, which otherwise cause “takeall” disease of wheat, or rotation of corn with beans in areas of Michigan can be used to reduce the fungal population responsible for bean-root rot. But it is no longer necessary to rotate other crops with legumes in order to enrich the soil with nitrogen. When these considerations are added to well-understood aspects of plant physiology, which dictate the manner of seedbed preparation, use of irrigation, density of planting, and soil salinity and acidity, soil management becomes an increasingly scientific enterprise, which feeds us today and assures that we will transmit this paramount heritage, the soil on which life depends, to future generations.

Meanwhile, the standing crop must compete with weed plants and survive its predators long enough to come to harvest. For centuries, manual and then mechanical hoeing required much of the farmer's labor. The discovery of a cheap chemical analog of the natural plant hormone auxin, 2,4-dichlorophenoxy acetic acid (2,4-D), in 1941 ushered in a new era. In low doses, this compound is highly toxic to some plants and innocuous for others. Ideally, of course, the former is the weed and the latter the crop. A great diversity of effective compounds allows the ideal to be approached, particularly where a broadleaf weed infects a gramineous crop or a grass infests a broadleaf crop, as is common. A series of congeners have since become available to spare the farmer in this classical task, because spraying with appropriate herbicides, tailored both to the major weeds and the crop to be spared, is even more successful than mechanical procedures.

Similarly, recognition of the insecticidal properties of DDT in 1939, initially used against insects directly injurious to man, indicated that intelligent application of understanding of insect physiology, entomology, pharmacology, and the arts of the organic chemist could prevent crop destruction by insects. To date, the use of 2,4-D has increased yearly even though it has been replaced in part, and DDT is being withdrawn because of concern for its potentially adverse effects on man, transfer to the general environment, prolonged persistence, destruction of beneficial insects and possibly other wildlife, and stimulation of resistance in the target insects. These are now matters of broad general concern, and it is regrettable that public decisions must be made on the basis of our limited knowledge. But these compounds paved the way for modern agriculture. Without their equivalent, modern intensive agriculture is not possible, and, just as the continual breeding of new crop strains is imperative, so too is a continuing search for effective herbicides and pesticides, optimally with specific effects on offending organisms, degradable in the soil and nontoxic to man and animals. Attainment of these goals will require continuously increasing understanding of plant and insect physiology and life cycles.

Control of undesirable species by biological means is, in many ways, the most attractive possibility for future exploration. The notion is by no means new; attempts at such control began late in the nineteenth century. Indeed, some 650 species of beneficial insects have been deliberately introduced into the United States from overseas, of which perhaps 100 are established. These are now major factors in the control of aphids and a variety of scale insects and mealybugs. More recently, microbes and viruses have been considered for these purposes, a few of which are being used; for example, spores of the bacterium B. thuringiensis are used to control the cabbage looper and the alfalfa caterpillar. Some insects have been utilized for control of weeds—e.g., prickly pear in Australia and the Klamath weed in the western United States—while a combination of the cinnabar moth and the ragwort seed fly is required to keep down the population of the toxic range weed, the tansy ragwort.

Still more imaginative and dramatic are such special procedures as the elimination of insect species, e.g., the screwworm, by introduction of sterile males (sterilized chemically or by gamma irradiation), thereby eliminating this longtime scourge of southern cattle; the use of minute quantities of synthetic or natural attractants, combined with an insecticide, have been used to eliminate the oriental fruit fly; and the setting of traps with flashing ultraviolet lights, which reduced the population of tobacco hornworm in some southern regions of the United States. The sterile-male approach is now being attempted for control of other insects, including some fruit flies and such devastating species to man and stock as the tsetse fly. Despite the successes in control of crop diseases and pests, losses are still serious, as can be seen from Table 4 . In the United States, much labor could be saved and product quality enhanced through better controls. In underdeveloped countries, the margin of safety between an adequate diet and malnutrition is so narrow that an unusual loss, as in a locust plague, is a disaster. At this time, it seems likely that current biological research will have some success even against the locust.

Crop Loss Due to Pests and Disease.

Each of these biological and chemical procedures has necessarily been the result of many years of investigation. Each is put into practice only when its consequences appear to be adequately understood. Yet each must necessarily alter the ecology of the affected region. When the pest species is successfully eliminated, some other species will probably take its place and may also require control. For the foreseeable future, the prospects are bright if the requisite research effort is maintained.

Animal Science

Meat and milk are important components of the total food supply. They provide protein of high quality and make otherwise uninteresting diets attractive. The herbivores, moreover, harvest the cellulose of plants, which man cannot digest. They can graze sparsely vegetated rangeland and can be brought to very high efficiency through management and use of biology. In the United States, more than two thirds of the total crop production is fed to animals.

Cattle, hogs, and sheep in the United States, taken together, total about 180 million, and there are twice that many chickens. The domestic animals of the Western World are the highly specialized results of careful breeding and selection. Biological understanding has been crucial to achievement of the desired goals of these breeding programs and will continue to be so.

No enterprise applies more science to the problems of breeding, nutrition, disease, and economics than does the poultry industry. Genetic improvement of poultry has yielded superlative results and holds even greater promise for the future. There is no reason to believe that the growth rate, efficiency of feed utilization, meat quality, and egg-laying capacity have reached the highest possible levels. In spite of much progress in disease control and nutrition, the mortality of older fowl is often, as high as 50 percent during the first laying year; since these animals are genetically capable of high egg productivity for two years, reduction of this mortality rate would yield great economic benefit. While chickens have been bred for high laying capacity and meat production, deliberate adaptation to diverse environments is only beginning. On a worldwide scale, geographical conditions of day length, temperature, humidity, and altitude warrant consideration in breeding programs if other nations are to share the boon of abundant inexpensive eggs and chicken meat.

In light of detailed understanding of chick nutrition and of the environment conducive to maximal growth and to egg laying, chicken growing has passed from an aspect of farming to a large industry, in which individual “chicken factories” grow tens of thousands of chickens simultaneously, each in its own enclosure, automatically fed, watered, and cleaned. In the most advanced practice, a computer program, containing the nutritional requirements of chickens and the composition of food grains, recomputes the most economic satisfactory mixture of cereal grains, based on daily or even hourly changes in grain prices and directs the mixing machinery accordingly. To be sure, this conversion to a chicken industry is not without cost. Such factories are deliberately located close to their urban markets. Grains are transported from their sources, but whereas the chicken farmer once returned the manure to the soil, it is uneconomic to transport manure back to Midwestern grain fields. The latter use chemical fertilizer while the manure accumulates outside the chicken factories, a problem not yet adequately managed.

When dependence on milk fat in the American diet was greater than at present, dairy-cattle breeders selected simultaneously for milk volume and high butterfat content. With increasing “calorie watching,” avoidance of saturated animal fats and acceptance of products based on plant oils, breeding attention has turned to emphasis on protein quality and content. Many genes control the various characteristics of cattle and, unless their heritability is reasonably high, selective breeding presents difficulties that will be overcome only with expanded knowledge of the mechanisms of genetic regulation. Attempts have been made to transplant the highly productive dairy animals of temperate zones to more tropical climates, where animal productivity is low and the need for dairy products great. These have failed; even when the cows themselves thrive, their milk production is dramatically reduced. But there is reason to suppose that genetic understanding, coupled with improved awareness of the environmental factors and the physiological response of milch cows to increased temperature and humidity will surmount the difficulty.

Like cattle breeders, swine breeders have been forced to react to increased consumer demands for unsaturated fats and avoidance of hard animal fat. Breeding for large deposits of fat beneath the skin and within the abdominal cavity is no longer profitable because a large portion of the market in which lard once brought high prices has been pre-empted by vegetable oils. Now, limited fat content, maximum muscle mass, and larger litter size are the important considerations, but crossbreeding has been less successful than commercial breeders had hoped. Again, one must turn to research for a solution.

The sea is one source of food that man has certainly not exploited wisely or fully. Today about 200 species of fish are used in the human diet. Their protein content is high and of excellent quality, their saturated fats meager. With few exceptions, including trout, salmon, and shrimp, fish are not harvested or farmed efficiently. Fishing is still a form of hunting economy. If fish farming were to be undertaken on an extensive scale worldwide, governments would be forced to reach clear and workable agreements governing fishing rights and territorial waters. And the scientific stage has not yet been set. Knowledge of the ecology of aquatic regions is inadequate to sustain much more extensive fish catches. Fish rearing, currently practiced for freshwater forms, is more art than science. The behavior patterns of fish species will have to be established, with knowledge of breeding grounds, reproductive potential, feeding habits, natural diseases, and predators. The females of many species produce millions of eggs. If adequate protection could be offered to fry and fingerlings, decidedly larger catches seem possible, based on current estimates of primary photosynthetic production at the sea surface. There is great potential for raising and stabilizing production by protecting the young of food species from hazards during this critical period.

But before such potential can be exploited, more thorough exploration of ecological factors must be accomplished. The consequences of introducing into the natural environment large numbers of certain kinds of animals with a high survival rate are not well known. There is a growing awareness that, even in the sea, the consequences of man-made changes in abundance can be far-reaching and not always to man's benefit.

There are other inadequately exploited opportunities. Shellfish could serve as an important source of dietary protein if full advantage were taken of available estuaries and shallow bays. Marine-biology stations have been studying the life cycles, physiology, and nutrition of such species for many years. Were legal obstacles removed and were there a genuine will to achieve these goals, a substantial industry could be established and improvement in human nutrition could result. There is reason to believe that several food species can be grown in inland impoundments. The per acre yield of catfish protein in Arkansas ponds is more than 10 times the per acre yield of chicken or beef protein. Current studies offer the prospect of success of shrimp culture in saltwater impoundments in areas such as the Louisiana bayou country. In each instance, long years of study of these species have prepared the way for an attractive future. But the task is by no means complete. Aquatic animals also are subject to diverse diseases; knowledge of those diseases is almost trivial, and knowledge of their control is even scarcer. Increased populations of edible pelagic fish must alter the ecology of a vast region, but with unforeseen consequences. Transplantation of major species from the Atlantic to the Pacific—e.g., shad and striped bass—has only occasionally been successful; each such trial must be followed closely for its secondary consequences.

One opportunity may already have been lost—the opportunity to harvest oceanic mammals, particularly some species of whales. These have already been overhunted. But it may yet be possible to manage the supply of the greatest of all animals in such a way as to utilize them as a steady supply of high-protein food.

Finally, it must be remarked that the marketing of fish offers special problems. Fish spoil readily; thus, processing plants must operate close to the sources and inspection procedures must be rigorous. A long-sought development now appears close to commercial realization. Fish-protein concentrate can be prepared from a variety of “trash” fish. An almost tasteless and odorless powder, it can serve as an important supplement to the diets of millions of malnourished individuals at very low cost. The alternative, enrichment of cereal flours with lysine, tryptophan, and methionine, may yet prove to be economically competitive, but both must be socially acceptable to the affected people. Meanwhile, the scientific bases for both endeavors have been well established.

We cannot close this subject without drawing attention to what should prove to be one of the major events in the history of human nutrition, already well under way—the “green revolution” —which consists in applying breeding and management to production of the basic grain crops in underdeveloped nations. The bleak image of lone farmers gathering meager crops is being supplanted in some areas by scenes of abundant harvest. Two to three years ago, for the first time since 1903, the Philippines produced more than enough rice for its own people, utilizing a new, short, stiff-strawed rice carefully engineered to thrive in Philippine paddies.

In the same year, India harvested a landmark crop of wheat, some of it the product of a sturdy short plant, bred for adaptation to the Indian farming milieu. Much of the harvest came from the north, from the fertile Punjab, but throughout the wheat-growing area, some fields were cultivated in the short new wheat, which yields 10 times or more the harvest of traditional varieties. In Pakistan and Turkey, farmers encountered similar success. In southern India, some farmers planted the new rice and were rewarded with abundant yields, as were Filipino farmers. To be sure, both crops were aided by a year of abundant rainfall. But the remarkable success of the new strains was self-evident, and the Indian Ministry of Agriculture declared that the nation had turned the corner to modern agriculture and predicted optimistically that within a decade India might be able to feed herself. A few hundred acres of new wheat were planted in 1964. By 1968, more than 20 million acres were under cultivation and plans called for 40 million acres in 1970. Withal, this represents only a fraction of India's farmland and is but a start.

The new wheats and rices emerged from painstaking crossbreeding with available strains to provide seeds that carry the most advantageous characteristics and with new mutants, each being examined for new useful properties. These new grains demand careful nurture. Designed to resist lodging, they also require and can make maximum use of fertilizers and water. They must be planted at the optimum moment and carefully tended. And, as in American agriculture, if the “revolution” is to be sustained, it will be essential that in these regions there be a continuing program of plant breeding to replace current strains as they fall victim to infection or pests.

The revolution began 30 years ago, when the Rockefeller Foundation sponsored a program to improve wheat and maize in Mexico. Through these efforts, the average yield per acre of wheat had been increased more than threefold by 1964. In 1959, the Rockefeller and Ford Foundations decided on a similar effort with rice, the staple food in the Orient. To this end, they established an International Rice Research Institute in the Philippines. The successful new rice varieties were bred there, drawing on the background of genetic information that had been accumulated in this country and Mexico. Success of the new varieties depends on packaging selected seed, fertilizer, and pesticides so that the farmer has these essential inputs at planting time. Perhaps the most significant aspect of this “green revolution” is that traditional farmers have been shown what can be done and are thus receptive to the further changes necessary to extend and stabilize these advances. There is no better illustration of the contribution of biological science to human welfare.

MAN AND His ENVIRONMENT

Science is applied to human affairs through an increasingly complex network of technologies. Each new technology finds acceptance if, for example, it solves a problem, eases a burden, enriches life, assures the food supply, or facilitates communication and transportation. But each such beneficial technology must be examined for its potential social cost. In this connection scientists must be particularly wary of threats to the public health, to the fertility of the soil, to the quality of air and water, and to the security of renewable resources.

Perhaps 500,000 distinct chemical entities and mixtures are in current use and hundreds more are added annually. Each must be considered for its effects on the biosphere, particularly on man himself—effects that may be acute, dramatic, and self-apparent or extremely slow, difficult to detect, and even indirect. For these reasons an increasing force of trained scientists is engaged in these activities. The level and pace of such activity are patently insufficient to the national need. Such agencies as the Food and Drug Administration and the Fish and Wildlife Service are seriously understaffed relative to national needs. Let us consider only a few pertinent problems typical of this large and disparate field of concern.

Water Supplies

Although it may not long be true, most American communities may still boast a supply of biologically safe water for domestic purposes. The character of the situation is such that potential hazards must be avoided from the beginning rather than removed after their introduction. The life scientist must be aware of these hazards, establish appropriate monitoring procedures, be aware of indications in the community of failure of controls, and establish reasonable standards. Avoidance of improper metals is now a long-established practice, as are a variety of procedures designed to minimize the presence of pathogenic bacteria.

That human disease can be transmitted through the water supply has been known in a qualitative way throughout history. Yet specific understanding of its role in disease transmission goes back only to the past century, with investigations of the spread of cholera and typhoid fever. Cooperative work by engineers, biologists, chemists, and physicians on the organisms responsible for such diseases and on development of methods for their control was so successful that these infectious diseases have been virtually eradicated from developed countries in which adequate treatment and sanitary control of water supplies are maintained.

Water can be freed of pathogenic microbial agents by (1) protection of water sources against initial contamination; (2) removal of organisms by filtration, adsorption, or similar physical means; and (3) chemical destruction of the organisms. All three approaches have been put under stress by increasing population density and demand for water. Because of these factors, coupled with a concurrent increase in sources of contamination— i.e., human and animal wastes—completely uncontaminated primary sources of water are becoming difficult to find.

As knowledge of the factors that affect the survival of waterborne pathogens and their sensitivity to various forms of water treatment increases, new methods of water management may well emerge. Research is needed to provide sanitary engineers with a rational rather than empirical basis for the design of facilities for collection, treatment, and distribution of water.

It has become apparent in recent years that traditional control measures are inadequate to prevent the spread of certain viral diseases that may be waterborne. Epidemics of infectious hepatitis have been known to be caused by water contamination. A most dramatic example was the 1956 epidemic in Delhi, India, where nearly 30,000 cases of hepatitis resulted from a temporarily contaminated water supply. There are now about 50 documented instances of similar, although much smaller, waterborne outbreaks of this disease, several in the United States. Because the hepatitis virus has only recently been identified and no animal other than man is known to be sensitive to this virus, thus precluding an animal model of the disease, there has until now been little opportunity to engage in the necessary studies.

Other viruses are assumed to be waterborne but have not been shown to transmit disease. With the possible exception of the polio virus, confirming epidemiological patterns have not yet been established. New techniques are required to gain definitive information about the health hazard these viruses present and the necessity for measures to remove them from communal water supplies.

Increasingly, water authorities must be aware of chemical contamination at the source, particularly by materials entering through groundwater or washed from the air by rain. Such materials do not announce themselves; one must be aware of the problem, perform appropriate analyses, establish standards, and, when feasible, institute procedures for removal of offending chemicals. Such actions may be taken on the general principle that no contaminants are acceptable, but there is greater conviction and urgency when the biological effects of a given contaminant are known. Most noteworthy, perhaps, are the various agricultural chemicals—insecticides, herbicides, and fertilizers. The soil burden of nondegradable insecticides is already such that they will be leached and present in communal waters for years to come. Current levels are such that no general risk is known to exist. Similar considerations apply to the herbicides. Although its teratogenic activity has resulted in a ban, 2,4,5-T concentrations in communal water supplies are trivial. The problems presented by fertilizers and nondegradable detergents are somewhat more serious. Nitrate from fertilizers, leached from manure piles or from sewage-disposal plants, occasions methemoglobinemia (the iron of hemoglobin is oxidized to the ferric state, Fe 3+ , in which condition it is useless for internal oxygen transport). Significant levels of methemoglobin caused by such contamination have been detected in various populations. No known deaths have resulted, and, in almost all such cases, it has been possible to trace the contamination and act accordingly. These incidents serve to point up the need for intelligent, biologically sophisticated management of water supplies.

The intensities of air pollutants in American cities today may be no greater than they were 25 years ago, except for a few areas such as Los Angeles or New York on bad days. But techniques for measuring the levels of chemicals or particulate matter in the air, then as now, were less than adequate. The most significant change in this quarter-century is that the American people are beginning to demand a higher level of quality in the environment. Levels of air pollution are difficult to measure, but new, sophisticated instrumentation is being developed. The body of knowledge concerning the biological effects of known pollutants is increasing but is unconvincing. Experience has shown that, when meteorological conditions heighten the concentration of atmospheric pollutants, individuals suffering from chronic lung disease and perhaps those with cardiac disorders may have serious reactions. Such episodes have no observable effect other than discomfort in the average, healthy member of the population, the individual of most concern to environmental biologists trying to evaluate the potential for serious consequences of long-term low levels of exposure. The most evident aspect of acute episodes of air pollution thus far is the increase in airborne sulfur dioxide and other sulfur-containing products from the combustion of coal and fuel oils. Normally less than 0.1 part per million (ppm), concentrations during prolonged inversions may rise to 0.5 ppm or more. Such concentrations are harmful to the most susceptible individuals and discomforting for the remainder. The fact that no evident illness is occasioned in healthy members of the population should not lead to a false sense of security. Effects not detectable by current procedures are not necessarily absent. In a few cases, toxic effects of pollutants have been documented. Beryllium, for example, is known to have produced serious disease downwind of beryllium-processing plants. Pollutants of well-established biological significance, e.g., carbon monoxide and lead, are being added to the atmosphere in immense quantities, primarily from automobile exhausts.

It is clear that all urban dwellers, because of the relatively high atmospheric concentrations of carbon monoxide, carry significant amounts of carboxyhemoglobin but not in sufficient quantity to limit physiological function. In episodes of striking increase, the consequence is an additional pumping burden on the heart, of no account in normal persons but perhaps sufficient to lead to serious crisis in those with incipient cardiac failure.

From epidemiological studies, the connection between cigarettes and lung cancer, heart disease, emphysema, and other diseases is now known. The carcinogenic action of cigarette smoke has been confirmed experimentally in animals, although specific chemical toxins have yet to be identified. Inhalation of smoke by rodents does not cause neoplasia; however, painting the tar of cigarette smoke on their skin is highly carcinogenic. There is a possibility that smoke contains agents that are not in themselves capable of producing cancer but that promote the growth of tumors by somehow interacting with otherwise innocuous doses of carcinogens. The causal relationship to cardiac disease is not understood. Nicotine does increase the oxygen requirement of the heart, while carbon dioxide from the smoke reduces the available oxygen supply, but these effects seem too small to account for known effects. Attempts to separate the effects of cigarette smoke from those of more general air pollution indicate a much higher correlation between smoking and disease than between community pollution and disease. It seems quite conceivable that a combination of cigarette smoking and general air pollution accounts for the higher statistical incidence of disease in the smoking population.

The necessity for monitoring the quality of air will not be lessened. New technologies will pose new hazards, and existing technologies will be used on larger scales. Thus, it is anticipated that combustion of fossil fuels for generation of electricity will quadruple by the end of the century, while that for transportation will double. Thus the potential gain from use of more efficient, less polluting automobiles may be totally offset by the increased level of use, a phenomenon demonstrated in the Los Angeles area.

Food and Drugs

Mounting concern with the effects of myriad chemicals in the environment has brought under closer scrutiny the agents that are deliberately added to food. Approximately 1,700 food additives are in use in the United States, and an equal number of additional materials go into animal feed and packaging materials. Each agent is subject to regulation by the Food and Drug Administration, which issues specific requirements to define closely the allowable concentrations of some agents and maintains a list of others that are “Generally Regarded As Safe” (the GRAS list). The safety of many of these materials that have enjoyed long tenure on the GRAS list is predicated on limited examinations performed years ago and on their long and seemingly innocuous usage by the public.

Safety is no longer easily assumed, nor is it a simple concept. When cyclamates—noncaloric sweeteners—were first introduced in the early 1950's, their use was limited to individuals who used them to sweeten coffee or tea. A decade later, the diet-soft-drink era came into being, followed by a mushrooming of the diet-food industry. The very fact that cyclamates were then consumed by many people in substantial amounts generated concern. Experiments voluntarily conducted by a pharmaceutical house revealed bladder tumors in a group of mice that had been fed vast doses of cyclamate over their entire life-spans (the equivalent of several thousand sweetened cups of coffee per day for man!). Although there was no evidence of similar effects in human beings despite the huge scale of the human “experiment,” according to the Delaney amendment to the Pure Food and Drug Act of 1958, any agent in food that causes cancer in any species, regardless of dose, must be banned. Cyclamates, therefore, were ordered removed from ordinary foods.

But this points up major difficulties. Where is the rational limit? How shall one balance the beneficial effects of voluntary caloric restrictions and avoidance of obesity by millions of Americans against the very remote chance of tumors in a few? By any seemingly reasonable standard, cyclamates had been adequately screened for toxicity until an almost absurd experiment was undertaken. It is noteworthy that, among the group of animals at half the tumor-producing level in the diet, absolutely no lesions were encountered! Quite conceivably, an equivalently rigorous and extensive review of the GRAS list will yield some similar experiences. When there is available a substitute that, by the same yardsticks, is innocuous, the course is clear. But when there is no substitute? This dilemma—risk versus benefit, and not necessarily to the same individuals—characterizes most major decisions concerning the environment. The difficulty cannot readily be mitigated, but certainly each such decision should rest on thorough understanding of the biological implications.

It cannot be assumed that toxicological data are adequate for many of the familiar chemical entities in the environment, let alone the scores of new ones. It was only 25 years ago that investigators learned of the effect of nitrate on hemoglobin. Recognition that cadmium in low concentrations in water may have adverse physiological effects and that some water supplies occasionally carry appreciable quantities of this element is even more recent. A Public Health Service standard for an allowable limit of cadmium was not set until 1962.

The task of the toxicologist is complicated by the fact that what is usually required is an analysis not of the acute effects of large doses but of the effects of very small doses accumulated gradually, of variability of response within a large population, and of the effects of other environmental variables and of disease. If there is evidence that a toxic compound accumulates in the body and that no tolerance develops to it or that its effects are irreversible, that agent is more menacing than one that can be detoxified or readily excreted or whose effects are reversed when it is removed from the environment.

The interaction of chemicals is often difficult to determine. The interaction of trace amounts, difficult enough in themselves to detect, compounds the difficulty, but can be of critical importance. A few years ago, it was found that when malathion and EPN (ethyl nitrophenyl benzytriphosphonate), both organophosphate insecticides, are fed together to experimental animals, the toxic effects are considerably greater than the sum of the toxicities of both chemicals. In consequence, the Food and Drug Administration issued a regulation requiring that each new organophosphate be tested jointly with every organophosphate already approved before the new insecticide is cleared for sale. The pyramiding of tests that this would engender is apparent. Relief came when the basis of this hazardous interaction was elucidated, thus permitting use of simpler means for predicting dangerous combinations.

Both of these insecticides are toxic because they inhibit cholinesterase, an enzyme essential to normal functioning of the neuromuscular system. Alone, malathion is only mildly toxic to mammals because it is itself destroyed by another group of enzymes, the aliesterases, before it can render extensive damage to cholinesterase. The aliesterases, however, are inhibited by EPN, thus opening the way for the total toxic effect of the malathion that accumulates. Understanding of the underlying mechanisms in this situation has permitted direct measurement of the effects of new pesticides by testing them against appropriate enzyme systems, offering a rational approach to the design of new pesticides.

The need to overcome similar problems in testing procedures and to acquire the ability to predict adequately what will occur in given situations is evident. Toxicologists, aware of their own limitations and responsible for protecting the public health, would have to lean on crude and cumbersome procedures to avoid any uncertainty about the safety of products they stamp with approval. But even excessive caution cannot guarantee safety if the substance of fundamental biological knowledge is inadequate. Results of extensive testing on animals may not be applicable to man. Thalidomide only rarely deforms unborn rats though it consistently deforms human beings. Relatively early identification of the effects of this compound in man must be attributed to the fact that it results in a deformity that is so rarely seen ordinarily that the problem was readily evident. Phocomelia, an anomaly in which the limbs fail to develop, is so rare a congenital abnormality that it immediately aroused suspicions of some environmental agent when the deformity began to appear in a relatively small number of infants. However, an agent without effect on experimental animals, but which induces diabetes in man, for example, would probably go undetected for a long period.

Extrapolation of animal data to man must be done with the utmost care and caution. One study comparing the reactions of rats, dogs, and human beings to six standard test drugs revealed many similarities, but of 86 distinct recorded effects, 33 appeared only in man! In the final analysis, after careful and extensive animal experiments have been completed, controlled human trials are imperative to measure the full range of a drug's effects. But, at present, these should be undertaken only after extensive trials with animals, tissue preparations, and, when appropriate, enzyme systems.

In the end, whether our concern be with drugs, food, or the physical environment, the hard question is what the American public is willing to pay for. Monitoring the environment while insisting on the right to drive one's own car is a costly matter. The more rigorous the standards, the more costly it must be. Similarly, the only effective approach to a multitude of disorders to which man is subject is the development of new drugs, which, in our society, is largely the function of the pharmaceutical industry. If these are to be thoroughly tested for safety and efficacy before they are marketed, the public must be prepared to bear the costs, not only of the marketed drugs, but also of the studies that discard those chemical entities that prove either unsafe or inefficacious. The biological capability, thanks to years of fundamental research, is well established. Although much yet remains to be done, a national capability for maintaining the human environment is attainable—providing we continue to train the manpower and bear the costs. What other alternative is acceptable?

RENEWABLE RESOURCES

The biological and physical elements of the earth are vital to man. Soil, water, air, and populations of plants and animals can, under certain conditions, be used over and over again. These are man's renewable resources, and their sound management has become a prime concern to man, both for his well-being and, perhaps, for his survival on this planet. The greatest single threat to environmental resources and to man himself is his own “population explosion,” with the concomitant rising pressure on food, land, and water needs. Only by understanding the function and interaction among biological and physical elements of the environment and applying that understanding to the management of resources can man control his numbers and keep his environment livable.

Although the major portion of man's food comes from only about 100 species of plants and animals, many thousands of species, including microorganisms, interact to provide the environment required by these major food sources. It has been estimated that at least 150,000 plant and animal species in the United States are involved in the collection and transfer of the sun's energy for the maintenance of life. In addition, some of these species are decomposers serving to break down waste products and dead organic material to make such essentials as carbon dioxide, nitrogen, and other elements available to plants for reuse and transmission to animals through the food chains of the biotic system. Beyond these material needs, living organisms are important in fulfilling esthetic and recreational needs.

Living systems have evolved for many millions of years to become a part of the environment as we know it today. Although civilization has developed throughout history at the expense of natural resources, population growth and technological achievements in the twentieth century have produced a disruptive assault on the environment on a greater scale than ever before. Contamination emanating from technological developments and urban concentrations has altered the chemical and physical characteristics of our seas, lakes, rivers, soils, and air. While simplified food chains have been exploited on some land to satisfy civilization's requirements for food and fiber, other vast land and aquatic areas have been developed for uses not associated with biological production. Economists project that within the next 20 years some 28 million acres (an area larger than Ohio) will be converted into urban areas and highways in the United States; four fifths of this land will come from croplands, pastures, and forests. Poor management in the past has resulted in loss of a third of the topsoil in the United States, with consequent lowered potential productivity.

It is difficult to return land to cultivation once it has been built upon. The quality of some of our surface waters and groundwaters can be restored, but, with the knowledge currently available to us, the results of pollution can be reversed only at great cost. For example, even if the introduction of fertilizing nutrients is terminated and if the waters of a historically heavily polluted lake can be completely exchanged over a period of time, the enormous amount of harmful matter bound in the bottom mud may continually replenish the pollutant materials.

How much more can we abuse our renewable resources—how much area can we remove from production, how many species can we destroy— before our resources will be unable to support man in an environment of acceptable quality? These crucial questions need answers now before renewable resources deteriorate irreversibly to an unacceptable level. We must maintain a continuing assessment of our renewable resources—land, water, air, and living things—because their status constantly changes. Only with such information can we find new and better ways to ensure their continuing availability.

Role of Science in the Management of Renewable Resources

The observations of early naturalists made important contributions to understanding of the environment. More recently, studies by pioneering systematists, geneticists, physiologists, evolutionists, and morphologists have provided much information of value to problem-solving ecology, although the significance of their contributions was not recognized for many years. During the past half-century or so, ecologists have searched for the principles underlying the interacting relationships of living things and their environments. Gradually they have come to recognize the complexity of these interrelationships and have categorized the influences on them as physical, biological, and, in some instances, social and cultural. Modern concepts of these dynamic arrangements recognize the constant interaction among all factors that make up the ecosystem.

Detailed studies of ecosystems or communities provide impressive demonstrations of mutual adaptation of species to one another and to their physical conditions. Host and parasite, prey and predator, and herbivore and plant are integrated in their life histories and requirements. These conditions can be understood in the light of modern evolutionary theory, which is based on genetic variability and natural selection and provides a satisfactory framework for understanding the diverse characteristics of the biological world. In this area, understanding and appreciation of population genetics is most critically needed. Understanding of the principles of natural selection is essential to the intelligent management of renewable resources, which almost always involves manipulation of populations by methods that depend heavily on selection of genetic traits governing such group properties as productivity, longevity, and reproduction rates. Ability to predict results will increase as more is learned about the mechanisms involved, both in the individual and in the interaction of populations.

Living organisms depend upon and are influenced by the physical and chemical elements of their environments. At the same time, they perform certain functions that are requisite to the structure and behavior of their physical environments—e.g., production of oxygen by plants through photosynthesis. Thus, understanding of the biosphere requires information about the physical nature of the environment (geology and soil science), the transport systems that move substances to and away from living things (meteorology and hydrology), the transformations that take place in the nonliving parts of the environment (physics and chemistry), and the means of modifying the environment (engineering, including weather modification).

Principles of Management

Rational plans for managing an environment either intensively (as in agriculture) or less intensively (as with wildlife) recognize that every area has a certain set of characteristics, that each living organism has a certain range of physical conditions that it can tolerate, and that for each physical condition there is some point or zone within the range that is near optimum. Organisms are aggregated into communities, the members of which are determined equally by their common ability to tolerate the physical conditions of the site and by their interactions with the other members of the community. The relationship is not passive, for the organisms in turn interact with and may change the site. Their tolerance levels are not necessarily identical, but they may overlap in the range of conditions present on a site. As conditions change, new forms, with tolerances that fall within the new ranges, may become a part of the community; some of those originally present may be eliminated. The less rigorous the conditions of the site the greater will be the variety of niches and inhabitants.

Two basic courses are open to us in using our surroundings: We can adapt our needs and demands to the capabilities of an area, or we can modify the area to change its capabilities. Urban and regional development, waste disposal without overloading the water or the air, and some recreational pursuits are examples of the former.

Environmental Management

Agriculture.

Agriculture has evolved beyond crop culture to become an environmental technology with emphasis on the management of land, water, air, and biological resources for the production of food and fiber and for the preservation of natural resources. The successful farm or ranch is, in fact, a well-regulated ecosystem in which renewable resources are effectively conserved. More than ever before in man's history, it is imperative to develop the technology by which agricultural practices can more effectively conserve our vast land, water, and biological resources.

Through sound management, agriculturists have been successful in making permanent use of renewable resources, especially land. In many places, the quality of the resources has been improved by careful use and management, with resulting increases in production and income. For example, in studies of individual farms in Illinois, yearly investments of about $35 per acre in conservation practices for soil and water returned about $41 per acre per year. Similarly, land that had yielded an average per acre of 15 bushels of corn, yielded 304 bushels per acre after six years of effective rotation and cropping practices. This kind of management makes possible the continuous and efficient use of the same natural resources year after year. In coming decades, with expanding world population, this aspect of conservation will become even more vital.

In sharp contrast is the unsound use of renewable resources that has led to disasters of the magnitude of the “Dust Bowl” of the 1930's. Before settlement in the 1870's and 1880's, the Great Plains had been protected against erosion during periods of drought by the natural cover of the short grasses. The first white settlers cultivated the land for wheat and in doing so destroyed the protective natural sod, exposing the bare soil to wind and other eroding forces until the soil structure was broken down. Thus, when severe droughts came in 1930 and 1931, soil conditions were ripe for devastation such as had never before occurred in the Great Plains areas. The Dust Bowl, involving 100 million acres, was a costly lesson to American agriculture; as a result of it, the Soil Conservation Service was formed in 1935 to devise and encourage sound land-management techniques. Only a small fraction of the Dust Bowl has been returned to production. Soil-conservation practices (contour farming, strip-cropping, rotation) illustrate effective use of applied ecology to maintain and even improve soil resources. Other ecological principles have been employed to increase crop and animal production but often have not been extended far enough to protect our renewable resources.

Water will always be a precious resource. In agriculture, much groundwater and surface water is lost or polluted by current practices. Manure, silts, and pesticides are some of the most serious pollutants. It is estimated that a fourth of all water stored for irrigation is lost by evaporation before use; yet water use in agriculture is increasing. Research has begun but more is needed to find ways to reduce evaporation of water in storage; some new chemical films offer considerable promise under special conditions.

Control of transpiration by plant hormones also offers a real opportunity to conserve water. This problem is well illustrated by the fact that, of the 500,000 gallons of water absorbed by an acre of corn in Illinois in one season, 498,750 gallons are lost to the atmosphere by transpiration.

Forestry deals with the management of wooded lands for various goods and services. The term “wooded lands” is liberally construed to mean forest landscapes, including areas of alpine rockland, native grass, brush, and swamps. Such areas often influence management of adjacent lands. Lumber production is the principal objective of most large corporate ownerships, but water yield, watershed protection, recreation, grazing, and protection of wildlife and scenic values are explicitly recognized on many private lands and are primary aims in the management of most public holdings.

The obvious economic value of lumber has led to a tendency among many conservation writers—including some foresters—to equate forestry with timber production. A century and a half of historical development, as well as present-day practice over large areas, has emphasized game production, stream flora, steep-land protection, and nontimber products. This emphasis finds its modern expression in the “multiple use” doctrine, which Congress has now declared to be the guiding principle for some 180 million acres of national forest. It is likewise espoused in varying degree by many public and private forest landholders. For example, revenues from hunting-club leases approximately offset land taxes on some industrial forest holdings.

In forestry practice, biology is the major but by no means the exclusive scientific tool. The earth sciences (geology, physiography, hydrology, climatology, and soil science), engineering, and a large economic, social, and managerial component often dictate the framework for biological applications. Protection from accidental fires has been the sine qua non of forest management through much of North America and necessarily absorbs a substantial part of the resources and technical effort devoted to forest land. The protection, manipulation, and efficient use of vegetation are the dominant aim of most forestry activities. Hence, an understanding of the dynamics of this vegetation and its associated populations of animals interacting with the physical environment is the forester's primary tool.

The need for applications of biology to forest-land management are more readily appreciated in view of the very different levels of management currently practiced. The most extensive management for wood products is simply exploitation of useful trees, usually with protection against severe fire and pests, with the hope of natural renewal. The input of biological skill is minimal, and the results range from excellent, as in many of the eastern Canadian spruce fir pulpwood cuttings, to the destruction of the resource. As intensity of management increases, measures such as restricted harvesting, timing of operations, prescribed fire, and thinning are employed to favor reproduction and growth of desired species and reduce competition with less valuable species. Such measures may be insufficient to perpetuate recalcitrant species, such as the American bald cypress or the New Zealand podocarps, whose regeneration requirements are neither met nor understood. At the highest intensities of management, desired strains are planted or otherwise made dominant, and density and structure as well as composition of the forest are closely controlled. For this purpose, the environment is modified by reduction of competition and pests, and sometimes by soil treatments.

At the lowest intensity of management, reliance upon natural processes is complete. At intermediate intensities, great dependence is placed on understanding the requirements of individual species, their competitive positions, and the nature of successional trends that may be either reinforced or combated. This concern diminishes at the highest intensities as regeneration, composition, and density are brought under control, with marked reduction in age and species diversity. Attention then shifts to altering genotypes, additional manipulation of soil and plant features, and specific measures against injurious insects and diseases.

True aquiculture, with complete control over all phases of a tended organism's life cycle, including a well-regulated harvest, has only regional importance (e.g., carp in the Far East and Israel, trout in North America and Europe). Fishery resources range from marine algae to whales and from the brook trout of alpine streams to benthic crustaceans at 200 fathoms in the sea. With few exceptions, fisheries are restricted to the lighted zone of the waters. Considering the gamut of aquatic plants and animals, the important species harvested are relatively few in number—about 200 among the over 20,000 kinds of fishes—and far fewer algae, mollusks, crustaceans, or aquatic mammals. Only 12 of these constitute 80 percent of the total catch.

Management for sustained yield is based on several factors, including (a) information about the stocks or populations and subpopulations that are often the effective breeding units (knowledge of age, growth, fecundity, longevity, and mortality due to natural causes and to exploitation); (b) information about the taxonomy, life histories, and behavior of the species under natural conditions and when confronted with capturing tools (included here are foods; food habits; sensory capacities; territorial or schooling behavior; knowledge of the action, including selectivity, of the capturing gear); and (c) information about the environment and the influences on the stocks of such variables as temperature, salinity, currents, and pollutants.

The deficiency in information needed for the adequate management of aquatic organisms can be ascribed to (a) lack of planning and failure of political boundaries to correspond to biological boundaries, (b) the short duration of studies in relation to the time span over which natural forces act and in which natural fluctuations take place, and (c) lack of funds, personnel, and interest.

The intensity of management measures applied to living aquatic resources decreases as the population dispersion and area occupied increase. Carp and trout, with their tolerance of confined freshwater areas, can be bred and tended intensively like domesticated animals with good control over their environment, while we can do little or nothing in the vast marine areas required by tuna or herring. With fishes of the latter type, management now depends upon prediction of population levels and controlled harvest. In the case of tuna in the Pacific, enough is now known about the relationship between tuna distribution and environmental conditions to permit satisfactory forecasts of distribution of tuna stocks several weeks in advance for the benefit of fishing fleets. Recent advances in tracing the life history of salmon at sea, coupled with detailed simulation models of the fishery, including the freshwater phase, provide an improved basis for prediction. Manipulation of spawning areas certainly provides opportunity for genuine management.

Management possibilities and the impact of man differ in the various regions of the hydrosphere. Fish and mammal stocks in the high seas can be managed only if characteristics of population and environment are known. Research on the high seas should be international in scope. Regional fisheries councils facilitate pelagic fisheries research. Agreements on apportionment of harvest through exclusive or joint exploitation are feasible. However, the common-property nature of high seas resources makes enforcement of harvest limitations difficult (e.g., only about 1,000 blue whales exist today). Furthermore, catch limits can be quickly filled with modern mechanized gear, and this leads to difficulties in keeping vessels and manpower profitably occupied, a problem encountered with the tuna stocks of the Western Pacific.

Offshore fish resources are most important in relation to bulk and dollar value. Such fishes as herrings, sardines, anchovies, and ground fishes (flat fishes) occur in abundance in various seas—the North Sea and the Caspian Sea for instance—and on the west coasts of certain continents, where currents and winds stimulate the upwelling and mixing of nutrients. Geographically, this region coincides with the continental shelf and overlying waters. Management in these areas, like that of the high seas stocks, must rely on regulation of gear and times of capture. More intensive methods of management are not presently feasible. There exist here common-property-resource problems that can be solved by bilateral agreements (e.g., Canada and the United States in the halibut fisheries). More and better agreements of this kind are needed; some may require new legal concepts because of the impending exploitation of this zone for other resources (minerals).

Near or inshore resources are often concentrated in shallow waters or near deltas and estuaries, or are associated with coral reefs. They are exploited by operators of small craft who, throughout history, have made up the bulk of the world's fishermen. Of the ocean environments, the inshore resources are most susceptible to overexploitation and to environmental deterioration caused by man. Along both coasts, estuaries are being filled with wastes at an alarming rate by industrial and housing developments. In addition, streams and rivers dump pollutants, collected from their drainage basins, into the estuaries. All this has already altered the ecology of these regions. Now many of these inshore resources will be subjected to further change by the addition of heated effluents from both nuclear and fossil-fuel power plants along our coasts. These plants require enormous quantities of water for cooling, and the low-grade waste heat carried by this water will also be enormous. If, for example, sufficient combined nuclear power and desalting plants were constructed on the West Coast to meet the needs for both fresh water and electric power, the rise in temperature of inshore waters might be as much as 4° F. Such a change in temperature would certainly alter the kinds, distribution, and abundance of animals inhabiting this area. We must be mindful of the opportunities to modify parts of this environment beneficially with this vast resource of low-grade heat, which could, with careless use, become a destructive pollutant. There is an attractive alternative, however—the use of this heat to maintain the environment of aquatic species that flourish in warmer waters, as has been done in England for cultivation of plaice.

The inshore marine environment, together with freshwaters that support the sport fisheries, suffer most from man's activities. Ecological imbalances resulting from events on the land are often difficult to correct, mainly because of traditional divisions in jurisdiction over and management of land and water. Authorities entrusted by society with the management of inshore waters have few or no organizational ties with those who determine land use, location and operation of industrial enterprises, and urban development.

Sport fishery in inland waters is strongly selective of predaceous fish (e.g., bass and pike) near the top of the food chain that constitute a small fraction of the total fish population available for harvest. Commercial fishermen stop fishing when it is no longer profitable. Anglers continue fishing for the large fish even though the numbers of fish decline and they have small chance of success. While the demand for large sport fish increases, the supply is limited. It may be preferable to modify the life habits of their predators, the anglers, so as to conserve the fish and their environment.

Wildlife may be defined as wild plants and animals in their natural environment (though often only animals are considered and here we consider mainly birds and mammals). The purpose of wildlife management is to maintain desired populations of wildlife. Wildlife management includes production and harvest of game species; maintenance of nongame species; and control of damage by wildlife to crops, forests, range, livestock, or human life. Management techniques have developed in a historical sequence that began with restrictions on time or methods of taking game, later included predator control and refuges, still later moved to artificial replenishment, and finally incorporated environmental manipulation.

Even though knowledge of habitat manipulation is considerable, we still rely on seasonal and bag-limit restrictions as the principal management measures for game species. Artificial game propagation attracts much public interest, but most wildlife biologists have come to regard this practice as better suited to intensively managed, private or commercial shooting preserves than to public hunting areas.

A great deal of the effort of fish and game agencies is directed toward gathering information on mortality, natality, and welfare factors that will be integrated to form the basis of the annual announcements concerning time and limits of harvest. Judgment gained from decades of trial and error still weighs heavily in the interpretation of field data; increasingly, however, sophisticated techniques are being employed. For example, in big-game management, many states conduct an annual survey of sex-age distribution in the population as well as estimating productivity from fawn-adult ratios and other population indices. Additional information on ovulation rate, placental scars, and weight and condition of carcasses is gained at hunter-checking stations. On many big-game ranges, annual surveys of forage are included as part of the information needed to establish the recommended harvest.

Habitat manipulation is potentially a far more responsive tool for managing areas intensively than is the regulation or restriction of harvest. Unfortunately, the manipulation of habitats is not feasible on some public and private lands, where other uses have high priority. The most successful widespread use of habitat manipulation came as a result of investigations in the fire ecology of the pinelands of the Southeast. Scientists have developed a high degree of skill in the use of fire in that region to manipulate forest communities for maximum wildlife production combined with timber or pulpwood production.

Among wild terrestrial vertebrates, particularly birds and mammals, much of the descriptive work at the species level has been accomplished, but many species occupying important niches over large areas are still little known. For example, until the appearance of a recent monograph, the mountain gorilla was largely a creature of mystery and misunderstanding. Similarly, the Wilson's snipe, an important migratory game bird in the United States, was largely unknown until a thorough field study of this species was completed recently. There are gaps in knowledge of some of the dominant members of the widespread communities in North America. For example, there is little knowledge of the actual effects of weather on deer, field voles, cottontail rabbits, and upland game birds, and of the physiological and behavioral adaptations of these species. The interactions among closely related species also need much more study. For instance, the effect of an expanding starling population upon other cavity-nesting species and the role of the starling as a vector of domestic-animal diseases should be studied more thoroughly.

The use of electronics, telemetry, and photography in remote sensing offers opportunities for real gains in dealing with wildlife problems. Research using some of these capabilities is under way, but progress is considerably short of what seems possible. The space program may launch a satellite with some components suitable for use by wildlife ecologists; however, many more applications are immediately feasible. For example, there are now microtransmitters with sufficient lifetime to permit following waterfowl or seabirds through an entire pattern of seasonal migration. With receivers that could be mounted in present satellite packages, continuous surveillance could be maintained on a sample of migrants fitted with microtransmitters. The same technique seems promising for marine mammals, large terrestrial predators, and wide-ranging ungulates.

Perhaps one of the greatest shortcomings in application of existing knowledge is reflected in the harvest of deer and other large ungulates. Satisfactory inventory techniques have been developed, but the public seems unconvinced of the high productivity of healthy deer in favorable habitats and fails to realize the resilience of a thriving deer population. Hunters, especially in the Northeast and Lake States, cling to their ideal of “bucks only” and frequently refuse to support a more flexible policy. The resulting underharvest of big-game herds has resulted in semipermanent damage to millions of acres of overutilized range.

Another area of confusion in applying research findings is in the control of pest animals. Numerous investigations have questioned the wisdom of pursuing traditional statewide predator control programs with little evaluation of either the need for the program or the effectiveness of the control effort.

Excessive populations of deer and elk are a nagging problem in national parks and on large military reservations, where hunting cannot be used to achieve population reduction. In these situations the use of chemosterilants offers promise of being a highly effectual technique. Considerable experimental research has already been done using these compounds on feral pigeons, gulls, and carnivores. This pattern of applied research should be extended to ungulates. Furthermore, increased effort in reproductive physiology would greatly enlarge our understanding of the effectiveness of antifertility compounds.

The effects of environmental pollution on wildlife is a subject of some importance. While the task of measuring direct effects of new spray materials is demanding, the subtle, pervasive phenomenon of bioaccumulation is of greater importance and is much more difficult to evaluate. The first step is to work out the pathways of pesticide-residue transfer and accumulation. The uptake, metabolism, and storage of pesticides are obvious objects for physiological studies that would support this effort. The ultimate fate of pesticide residues would be much better understood if concepts of major drainage basins as ecosystems were more clearly defined and described. The monitoring of pollution loads would be greatly expedited by advances in analyzing ecological systems.

Provision of adequate opportunities for outdoor recreation requires an understanding of the needs and desires of the potential participants, the kind and location of environment that will meet these needs, and the effects of use on these environments. Until we understand better why people seek outdoor recreation and the motivation that determines their recreation choices, and until there is general awareness of the deleterious effects of recreational activities upon the natural scene, much restorative effort will be of the stopgap variety. But treatment of the symptoms does not identify and eliminate the cause; thorough knowledge of the physical and biological components of the recreation environment is imperative. Equally necessary, however, is a deeper understanding of human behavior.

In many instances, biologists and other recreation-resource managers have not considered the visitor and the resource to be part of the same ecological situation. The use of the term “visitor,” in this case, may be unfortunate. Nonetheless, at a time when perpetuation of the resource depends in part upon the visitor's understanding and cooperation, he and his fellow citizens, many of them urbanites, seem uninformed and careless about soils, plants, animals, and their interrelationships.

The recreation visitor and his activities influence not only the immediate site being occupied but also the adjacent areas that form the scenic backdrop. His presence may generate problems beyond those that already exist. Wilderness areas and national parks are good examples in which visitor-recreation problems extend beyond the immediate site being occupied. Although many such areas are more than several hundred thousand acres in size, the direct physical contact of visitors is concentrated on a very few acres. Within these small areas of intensive use, vegetation is trampled, soils are compacted and eroded, and water supplies are subjected to pollution. Overuse and abuse—albeit unintentional—prevail. Further, these sites of intensive use are often in aesthetically pleasing but fragile areas least capable, biologically and physically, of withstanding great visitor pressure. To a certain degree, the selection of such sites is a result of uninformed management or poor planning of land use. There is some evidence, however, that these are the kinds of areas that many visitors—the recreation public—prefer. To be sure, some persons wish to camp in relatively isolated sites in more stabilized vegetation systems regardless of the lack of modern conveniences. However, most recreation campers prefer to congregate in high-density campgrounds where electricity, sanitary facilities, hot and cold water, cooking accommodations, and other refinements are available, and where the vegetation is in a highly vulnerable, unstable stage of development.

In periods of peak activity, present ability to handle the masses of out-door-recreation enthusiasts is rapidly becoming quite inadequate. The number of visitors to our national parks and national recreation areas begins to pose a serious problem ( Figure 32 ). The visitor load in these public areas has increased nearly sixfold in 20 years and in 1968 was 151 million; the number of parks has increased at a much slower pace. Indeed, the number of units in the national park system, including national parks, monuments, seashores, and historic sites, has increased only 50 percent in this period. Potential sites for additional large-scale and magnificent recreation outlets are not unlimited. If visitor pressure on national forests, other wilderness areas, and state or local recreation facilities follows the general pattern experienced in the national parks, and if there are not substantial changes in the concepts of visitor management, we are clearly in danger of running out of space for certain types of recreational activities.

Total visits to national parks and related areas, 1950–1968, and projected visits to 1975. (From Biology and the Future of Man, P.Handler, ed. Copyright © 1970 by Oxford University Press, Inc. Data from Statistical Abstract of the United (more...)

On wild lands managed for several purposes, the need for both more thorough ecological understanding of the landscape and greater insight into the physical requirements of an attractive landscape is coming into sharp focus. Much of the public seems more concerned about the “visual resource” than about the physical resource. The outdoor-oriented American public evidently does not wish to become reconciled to the fact that natural processes must sometimes be accompanied by temporary ugliness. Yet good silviculture may entail controlled burning to permit regeneration of more desirable trees, burning to maintain a plant community characteristic of a true prairie, reduction in an elk herd to forestall starvation of the animals and destruction of their range, or introduction of native predators to assist in the control of big game or other animal populations.

URBAN AND RURAL DEVELOPMENT

Man needs dwelling places, stores, industries, schools, museums, places of worship; he needs arteries for transport by rail or motor vehicle; he needs airports, canals, harbors, and dams. Once land is committed to these uses, the commitment is essentially irreversible. Man's activities in these places change raw materials and natural products into new forms, often resulting in waste products that must somehow be disposed of or recycled. When these waste products reach the air or water or land in forms or concentrations that are detrimental, they are “pollutants.” Unacceptable means of waste disposal are the cause of one of the major impacts of man on his environment.

With increasing numbers of people, needs for food, fiber, industry, and transport—indeed for all kinds of goods and services—increase. Expansion of our cities converts more than a million acres of land a year to paved, biologically unproductive areas. At the same time that command of enormous amounts of energy for excavation, construction, and earthmoving gives ever greater freedom of choice in the location of cities and changes in the landscape, the changes are, all too often, unplanned and unthinking. The big changes—canals and dams, perhaps even interstate highways— are considered with some care, and the more obvious costs and benefits publicly weighed. The results are not always those biologically most desirable, but they are, for the most part, democratically acceptable. The more pervasive and uncontrollable changes result from incremental changes, as in creeping suburbia and filled-in wetlands. No single acre in these latter categories elicits much public defense, but the aggregate loss exceeds what we should be willing to accept.

In urban renewal or modification of existing metropolitan areas, the problem is to make the “best” use of the area. Zoning is useful to this end. Heavy, dirty industry can be positioned in relation to dwellings, open space, and other living parts of cities so that air pollutants are carried away, noise does not reach the dwellings, and offensive odors and the grime of industry are out of range of the senses of most inhabitants. Some trees, shrubs, and other plants will tolerate even existing congested and polluted conditions, and can thus be used for beautification. Transportation and communications systems can be planned so as to minimize conflicts among the diverse demands of metropolitan life.

The imminent location and construction of whole new cities affords both superb opportunities and difficult challenges. Before the turn of the century this nation will need to provide housing for an additional 100 million people, or a population equivalent to the sum of 500 Restons, 100 Columbias, 50 Atlantas, 5 Philadelphias, and 5 New Yorks. This new housing may either sprawl and congest the surroundings of existing cities or start afresh in entirely new locations. Much less concern will be necessary than heretofore with the needs for transportation and communications or nearness to primary resources. Locations can be based upon the amenities; water, raw material, and various modes of transportation can be brought to them as required.

Whether present cities are expanded or entire new ones built, it is imperative that their effects on the environment be considered. Paving of groundwater recharge areas, scalping of steep slopes, and placement of septic tanks in impermeable soil can all be avoided. Waste-treatment facilities can improve rather than damage their surroundings. Planners, architects, and engineers will be largely responsible for appropriate use of the environment. Development of understanding of land-use capabilities and a reciprocal interaction between the desired design and land-use-capability criteria will permit optimum use of the environment.

Local governmental and federal agencies should recognize a public right to live in an environment of acceptable quality. The true costs of any program in the management of renewable resources, be it in industry, agriculture, recreation, health, forestry, fisheries, or urban development, should be evaluated, and decisions should be made, upon the advice of groups of specialists, by representatives of society as a whole, seeking what is best for local, continental, and planetary ecosystems. Only by knowledge and understanding of the function and interaction of the biological and physical elements of the environment and by application of this knowledge and understanding in sound management programs can man expect to conserve the natural resources that are his great heritage.

INDUSTRIAL TECHNOLOGY

Biological science finds application in many aspects of the economy. There is no precise biology-related equivalent of the chemical or electronics industries, which bear one-to-one relationships with specific areas of science. As we have seen, agriculture, medicine, protection of the public health, and conservation of renewable resources all directly apply increments in biological understanding. Here we shall indicate briefly a few additional industries whose capabilities, scale, and quality rest on applied biology.

Pharmaceuticals

Reference has repeatedly been made to the role of the pharmaceutical industry; suffice it to note, then, the magnitude of this industrial endeavor. In 1967 the industry had gross sales of about $4.2 billion. Of this, 10.5 percent was allocated to its own research and development programs— about one fifth of the nation's entire biomedical research enterprise—in which just under 20,000 scientists and supporting personnel were employed. Table 5 summarizes the categories of drugs sold in 1967. The magnitude of the research task is shown by the number of animals required ( Table 6 ).

1967 U.S. Drug Shipments in Major Categories (In $ Millions).

Animal Usage in the Pharmaceutical Industry in 1965.

By now, the general pattern of pharmaceutical research is somewhat standardized. Research directors, aware of the needs of human and veterinary medicine, monitor the output of worldwide fundamental biomedical research for clues to potential new drugs. Chemists then either purify some naturally occurring material or synthesize a desired chemical entity and a series of variations on this theme. The potential drug is then put through a “screen,” an increasingly large and diverse battery of biochemical and physiological tests. If the material still appears to have the desired activity, it is tested in animal models of the human disorder, where such exist, and then screened for short-term and long-term toxicity in a variety of animal species. If all appears to be in order, permission is requested of the Food and Drug Administration to test the drug in man. After a tolerable dosage level is established in a few subjects, a much wider group of patients is treated with the drug for its specific use, while also being observed for any signs of toxicity. When a sufficient series has been tested, if the drug has proved efficacious for its intended purpose and if undesirable side reactions are minimal, permission is sought for free marketing. Finally, the Food and Drug Administration must balance hazard against benefit as it comes to a decision. No foreign compound is totally devoid of untoward effects. Indeed, were aspirin invented tomorrow, the Food and Drug Administration would have a difficult time in deciding whether to issue a license. If the benefits warrant and the hazards are tolerable—particularly if the drug offers decided advantages over existing drugs or is truly lifesaving—the Food and Drug Administration will issue the desired license, about 5 to 10 years and $5 million to $10 million after the start of the project.

The overall results are evident in the facts that no more than 10 percent of drug sales represent entities available before 1940, that mortality from all infectious diseases fell from 88,000 deaths in 1941 to 17,000 in 1961, that tuberculosis sanitariums are closed, tranquilizers have emptied thousands of sanitarium beds, and few of us any longer are asked to bear extreme pain, thanks to nonaddicting, powerful analgesics.

Once harvested or slaughtered, the products of agricultural practice must be “brought to the table.” This is accomplished by the many components of the food industry, employing 14 percent of the working population in an endeavor aggregating $90 billion in 1966. Through the combined efforts of applied biologists, chemists, and engineers, the housewife may now choose among 8,000 items in the supermarket. This team has solved the problems of raw storage; out-of-season processing; long-term storage; minimization of contamination by agricultural chemicals, bacteria, yeast, and molds; maintenance of moisture and nutritional content. It has upgraded the nutritional value of various native foods; monitored all stages of the preparative and marketing process; established the optimal conditions for transport and storage; devised such preservative mechanisms as ethylene oxide, sulfur dioxide, and nitrogen gas atmospheres, as well as procedures such as vacuum-, spray-, drum-, and freeze-drying, while monitoring such processes as fermentation of sauerkraut, cheese, or buttermilk and sterile filtration of beer, wine, and fruit juices. It has devised the wide variety of food additives now available and has developed specialized foods for diabetics, phenylketonurics, and galactosemics, as well as for those with heart or kidney disease or gastrointestinal limitations.

As noted earlier, the properties of DDT and 2,4-D inaugurated a new era in management of our living resources and gave rise to a new industry. Each touched off a wave of research that continues to the present, seeking newer compounds that are species-specific, safe, and degradable. For the moment, the use of such compounds is indispensable; until superior means and materials are found, these compounds are essential to the success of our agriculture, while assisting in maintenance of our woodlands and protection of our health. It is the scale of this use, rather than their intrinsic toxicity, that has properly generated public concern over the effects of these chemicals on the public health. In 1966, total production of all pesticides in the United States was 1,012,598,000 pounds.

The rapid increase in use occurred because new pesticides have been developed that control hitherto uncontrolled pests, and broader use of pesticides in large-scale agriculture has increased crop yields significantly. Current trends in crop production involving large acreages, greater use of fertilizers, and intensive mechanized cultivation and harvesting offer particularly favorable opportunities for insect pests and would result in large crop losses to these pests unless control measures were applied.

The increased number of new pesticides in part reflects a second generation of pesticides with more appropriate persistence for economic control of specific pests, more complete control of the pest, less hazard for the applicator, or less hazardous residues on the crop. An additional impetus to the development of new pesticides comes from the fact that many insect pests have developed resistance to the older pesticides. The development of pest resistance does not necessarily entail the development of more dangerous pesticides; the new agent need only be chemically different to overcome resistance. The continuing search for new, more nearly ideal pesticides requires the joint effort of research teams composed of organic chemists, biochemists, pharmacologists, physiologists, entomologists, and botanists. The effort is managed much like the development of new drugs, each chemical entity being tested in a “screen” of a variety of insects.

About 73 percent of the total insecticide usage is in agriculture, and about 25 percent is used in urban areas by homeowners, industry, the military, and municipal authorities. The remaining 2 percent is applied to forest lands, grassland pasture, and on salt and fresh water for mosquito control. Over 50 percent of the insecticide used in agriculture is applied to cotton acreage alone.

When insect-control measures are not used in agriculture, insect pests take 10 to 50 percent of the crop, depending on local conditions. Losses of this magnitude are not readily tolerated in the United States in the face of a rapidly increasing population and a concomitant decrease in agricultural acreage. In this sense, the use of insecticides might be deemed essential at this time for the production and protection of an adequate food supply and an adequate supply of staple fiber. While alternative methods of pest control are under investigation and development, they are not yet ready to displace completely the chemical pesticides, and it appears that a pesticide industry will be required for some years to come.

Pesticides have been tremendously effective, but individual pesticides, like sulfa drugs and antibiotics, tend to lose their effectiveness as species resistance to them develops. Hence, there will be a continuing search for new pesticides as long as pesticides are considered to be required for the economy or the public health. This search will require the continuing participation of able biologists. As with drugs, new pesticides, optimally, should be selectively toxic for specific pests, rather than broadly toxic against a wide variety of pests with serious side-effects on nonpest species. Broad-spectrum pesticides affect an essential enzyme or system common to a wide variety of pests. A selective pesticide, on the other hand, either should affect an essential enzyme or system peculiar to a particular pest or should be applied in such a way that only the particular pest gains access to it.

An interesting example of a selective pesticide is the rodenticide norbormide, which is highly toxic for rats, particularly for the Norway rat. By contrast, the acute oral toxicity of norbormide for other species is much lower, the lethal dose for a great variety of birds and mammals, per kilogram of body weight, being more than 100 times greater. The mechanism of the selective toxic action of norbormide for rats is not yet elucidated.

Achievement of target specificity requires a sophisticated knowledge of the anatomical, physiological, or biochemical peculiarities of the target pest as compared with other pests or vulnerable nonpests; a pesticide may then be developed that takes advantage of these peculiarities. This is obviously not easy to accomplish, and norbormide may prove to be unique for many years. An alternative is the introduction of a systemic pesticide into the host or preferred food of the target pest. Other pests or nonpests would not contact the pesticide unless they shared the same host or food supply. As an example, a suitable pesticide may be applied to the soil and imbibed by the root system of a plant on which the pest feeds. The pest feeding on the plant then receives a toxic dose. The application of attractants or repellents (for nontarget species) would increase the selectivity of the systemic pesticide. The use of systemic pesticides on plants used for food by humans or domestic animals poses an obvious residue problem.

There has been a strong public reaction against the continued use of pesticides on the grounds that such use poses a potential threat to the public health as well as being a hazard to wildlife. Careful investigations have so far failed to establish the magnitude of the threat to the public health; i.e., there are as yet few if any clear-cut instances of humans who have suffered injury clearly related to exposure to pesticides that have been used in the prescribed manner. Report No. 1379 of the 89th Congress (July 21, 1966) * concluded:

The testimony balanced the great benefits of disease control and food production against the risks of acute poisoning to applicators, occasional accidental food contamination, and disruption of fish and wildlife…. The fact that no significant hazard has been detected to date does not constitute adequate proof that hazards will not be encountered in the future. No final answer is possible now, but we must proceed to get the answer. (Italics ours)

Failure to establish such hazard does not mean that it does not exist. There are no living animals, including those in the Antarctic, that do not bear a body burden of some DDT. Large fish kills and severe effects on bird populations have been demonstrated. The large-scale use of these agents has been practiced for less than two decades, and use has increased annually until this year (1969). Whereas the anticholinesterase compounds, which have high acute toxicity (and hence are highly hazardous to the applicator), are readily and rapidly degraded in nature, the halogenated hydrocarbons are not. With time, their concentration in the soil and in drainage basins, lakes, ponds, and even the oceans must continue to increase, thereby assuring their buildup in plant and animal tissues. Over a sufficient time period, this is potentially disastrous. And should such a period pass without relief, the situation could not be reversed in less than a century. Because of the large economic benefit to the farmer, it is pointless to adjure him to be sparing; unless restrained by law, he will make his judgment in purely personal economic terms. But mankind badly needs the incremental food made possible by use of effective pesticides, and the enormous benefit to public health of greatly reducing the population of insects that are disease vectors is a self-evident boon to humanity. Thus it is imperative that alternative approaches to pest control be developed with all possible dispatch, while we learn to use available pesticides only where they are clearly necessary and desirable and to apply them in the minimal amounts adequate to the purpose.

A recent development in insect-pest control has been the possible use of juvenile hormone. This hormone, normally produced by insects and essential for their progress through the larval stages, must be absent from the insect eggs if the eggs are to undergo normal maturation. If juvenile hormone is applied to the eggs, it can either prevent hatching or result in the birth of immature and sterile offspring. There is evidence to suggest that juvenile hormone is much the same in different species of insects, and analogs have been prepared that are effective in killing many species of insects, both beneficial and destructive. There would, therefore, be great danger of upsetting the ecological balance if juvenile hormone were applied on a large scale.

What is needed, then, is development of chemical modifications of juvenile hormone that would act like juvenile hormone for specific pests but not for other insects. For example, a preparation from balsam fir, which appears to be such an analog, has been identified and is effective against a family of bugs that attack the cotton plant, but not against other species. If it proves possible to synthesize similar analogs specific for other pests, a new type of pesticide may emerge. If this happens, it will be extremely important to explore possible side-effects on other insect species and on warm-blooded animals before introduction of yet a new hazard into the biosphere.

We cannot rest with existing pesticides, both because of evolving pest resistance to specific compounds and because of the serious long-term threat posed by the halogenated hydrocarbons. While the search for new, reasonably safe pesticides continues, it is imperative that other avenues be explored. It is apparent that this exploration will be effective only if there is, simultaneously, ever-increasing understanding of the metabolism, physiology, and behavior of the unwanted organisms and of their roles in the precious ecosystems in which they and we dwell.

Fermentation Industry

Wine and leavened bread date back to antiquity, but the fermentation industry is a product of modern biological science. In sum, the disparate fermentation industry constitutes a major national resource. Each of the major companies in that industry retains a staff of microbiologists, biochemists, chemists, and engineers. Together, they are responsible for the continuing monitoring control of the fermentations with which they are concerned. The microbiologists constantly search, by the conventional techniques of bacterial genetics, for new strains of micro-organisms that will more efficiently or more rapidly conduct the fermentation in question. Rarely do these groups, as such, discover new fermentations yielding new products of value. Most have been encountered earlier in the course of systematic microbiology, and the industrial research team develops the procedures whereby a laboratory observation is scaled up to the requisite industrial magnitude. An important exception has been the systematic hunt for new antibiotics by the drug companies.

Bakers', food, and fodder yeasts were produced in excess of 180,000 tons in 1967. Alcohol fermentation amounting to 685 million gallons in 1945 has largely been replaced by a process starting with petroleum-cracking fractions, as has the fermentative production of acetone and butanol. But 5 billion pounds of raw grains were used to produce 110 million barrels of beer and ale, while 235 million gallons of wine and 185 million gallons of distilled spirits were also produced by fermentation. Other fermentation procedures produce lactic acid, vinegar, dextrans for drilling muds and as a plasma substitute, sorbose, and glutamic acid. Bacteria are grown as legume inoculants and as bioinsecticides. Molds and streptomyces are grown as a source of at least 30 distinct antibiotics in general use, as well as of citric acid and a variety of other organic acids. One mold is now used to make giberellin, which stimulates seed germination, improves growth of young trees, increases the flowering of plants, “sets” tomato fruit clusters, and breaks the dormancy of potatoes.

Allied to these processes is the use of molds, streptomyces, and bacteria in synthetic chemistry to accomplish specific reactions not readily feasible by chemical means. At least 25 such procedures are in current use in steroid synthesis in pharmaceutical laboratories. Related, also, is a relatively new industry, the manufacture of enzymes on a substantial scale. At least 20 enzymes are now articles of commerce. Thus, amylases from pancreas, barley malt, or fungi are used to de-size textiles, start brewing fermentation, precook baby foods, or cold-swell laundry starch. Papain from papaya, bromelin from pineapple, and subtilisin from B. subtilis are used as meat tenderizers, to stabilize chill-proof beer, and most recently as adjuncts to laundry detergents. Still other enzymes are used in candy manufacture, in clinical diagnostic procedures, to clarify wine and beer, to tan leather, and for debridement of wounds. The list of enzymes and their uses is growing, limited only by imagination.

No estimate of the magnitude of these diverse biological industries is available, but clearly in sum they represent several billion dollars of the gross national product. In every instance, biological understanding underlay the original industrial concept, guided the necessary research and development, gave direction to the industrial installation, and is required for continuing monitoring of the process.

Instrumentation

The scale and sophistication of modern biological research and its applications have necessitated birth of a new industry—the manufacture of biological instruments. The need for and use of most instruments usually arises in a research laboratory. But, thereafter, if it is to be more generally available, conveniently packaged, simple and reliable in performance, and readily serviced, its production must be taken over by a commercial manufacturer. Competition among manufacturers is the stimulus that has provided a stream of increasingly useful, sensitive, and reliable instruments, annual sales of which now approximate $1 billion. Appreciation of the diversity of such instruments may be gained from the data concerning use and need presented in Chapters 3 and 4 .

When established, such instruments are modified to monitor and control industrial biological processes and for diagnostic and therapeutic use in hospital practice. An excellent example is the development of an automated apparatus that can accept an unmeasured small volume of blood, perform about 15 different analytical procedures thereon, calculate the results in conventional units, and record them on the patient's record. These data are decidedly more reliable than are individual determinations performed manually by technicians, and the cost is comparable to that of a single such manual procedure. In consequence, the physician's armamentarium is markedly expanded, at no additional cost to the patient or to society.

From this brief summary it will be evident that the skills and understanding of the modern biologist find their way into a remarkable variety of human endeavors, rendering life more secure, healthier, longer, more comfortable, and more pleasant, while giving employment to millions.

U.S. Congress. Senate. Committee on Government Operations. Interagency Environmental Hazards Coordination, Pesticides and Public Policy (Senate Report 1379). Report of the Subcommittee on Reorganization and International Organizations (pursuant to S.R. 27, 88th Cong., as amended and extended by S.R. 288), 89th Cong., 2d sess., Washington, D.C., U.S. Government Printing Office, 1966.

Cite this Page National Academy of Sciences (US) Committee on Research in the Life Sciences. The Life Sciences: Recent Progress and Application to Human Affairs: The World of Biological Research Requirements for the Future. Washington (DC): National Academies Press (US); 1970. CHAPTER TWO, BIOLOGY IN THE SERVICE OF MAN.

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ASL Topic n Short Essays with Example on – Science in the Service of Man

science in the service of man.

(The following speech is perfect for 1 min. to 1.05 min)

The first scientist was the caveman who picked up a stone to kill a deer- he made something to serve his purpose. Science made advancement in the sharpening of stones to serve as weapons, making fire by striking one stone against another. Man gradually made machines to serve him and today these machines are so much with us that we cannot do anything without them. Science is all around us. We are living in an age of science. It is difficult to think of human progress without scientific inventions. These inventions have brought about a great change in the life of a man. Wonderful inventions in medicine and surgery have made life healthier and happier. Diseases which were considered to be incurable in the past are today easily cured. Plastic surgery and transplant of such vital organs as heart and kidney are of great help. Inventions in the field of transport and communication have conquered time and space. Isn’t it thrilling to watch a cricket match being played in England or Australia in our drawing room telecasted with the help of satellite?

Q. Do you really think that science helps us without any harm? A. Actually, I am partially not convinced with your view as I think that science is a good servant but a bad master and it is up to us that we become the slaves of it or treat it as a servant. Excess of everything is bad.

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Essay, Paragraph or Speech on “Science in the Service of Man” Complete Essay, Speech for Class 10, Class 12 and Graduation and other classes.

Science in the Service of Man

Essay No. 01

Facsimile (Fax)—Facsimile transfer of messages i.e. is used for transmission of weather charts, engineering drawing and even hand written notes. It transfers copies of any types of document written in any language and in any script with a great speed. The Fax employs a photo-scanning process to obtain its electrical signals which are then transmitted through the communication channels at the receiver end, the message is automatically printed on a laser printer. The equipment in which the document is placed is called POTS.

Pager—It provides one way wireless communication to the wandering users. In this system, the messages are sent to the subscribers which consist of a small receiver. The messages that can be sent are of three types.

(a) Only ton beep is given

(b) Numeric message—in which the telephone number of the cellar is transmitted to the subscriber (i.e. receiver) and

(c) Alpha-numeric message in which the message in alphabets numerals is transmitted. The cellar calls the base station (B.S.) and gives them message and destination cellphone or pager number. The base station then sends the message to page subscriber through wireless technology. The receiver units responds to a short burst of coded signals of beeping and activating a vibrator to indicate that he is wanted.

LASER— The name LASER is an acronym for light Amplification by Stimulated Emission of Radiation. A Laser is an electric apparatus for producing unified light waves that can be exactly controlled, precisely focussed and when desired made extremely powerful. It can be aimed precisely enough to destroy dangerous skin tumours without affecting healthy skin tissue. Laser light has certain remarkable properties which make it chromatic, for example, a red laser beam has only red light. Laser is very coherent and can be transmitted over great distances, without the beam spreading. It also has the advantage that a lot of power is concentrated in a very small area. Sunlight electric light and the light from a candle is incoherent. It is a jumble of different wave length and brightness in what seems to a steady light emitted in every direction. To produce a coherent beam, the original light has to be coherent and that is what a laser does.

Initially, the lasers used rubycrystals and were not very powerful, fairly expensive and unwieldy. The present day lasers come in all sizes ranging from the micro-lasers to the huge lasers used for fusion research.

Robotics— Robotics is the study of the design and use of robots (Czech; robot meaning compulsory service) i.e. the machine programmed to carry out a series of operations without human guidance. The word Robotics was invented by Isaac Asima. Industrial application of robots is favoured because of their untiring nature, predictability, precision, reliability and ability to work in relatively hostile environment. Besides robots frequently increase productivity, improve overall product of quality, allow replacement of human labour in monotonous and of course in hazardous task. Computer controlled robots are used in industry to do welding, assembling and machining and to handle various materials. Non-industrial applications of robots include marine space work bionomics, form work, helping the disabled, lab work, mining, nuclear work, security guarding simulation, warehouse, microsurgery etc.

Polymorphic Robot – Recently the scientist have developed a polymorphic robot, which can change its shape according to the job that it is assigned to. The thermoplastic framed robot is being developed by HodLipnn with Jordan Pollock. The basic idea is to assign the robot a particular task, and then a computer would attempt to design a specific body, which would facilitate the robot to meet this challenge with efficiency.

RADAR—Acronym for Radio Detecting and Ranging (RADAR)—a technique and apparatus for determining in the location of an object by the use of radio-waves. The most visible and ubiquitous aspects of radar are the rotating curved surface, antennas seen on the top of most ship and airport towers. Not visible but equally important are radar antennas hidden in the noses of aeroplanes.

It is a system employing microwaves for the purpose of locating identifying, navigating or guiding such objects as ships, aircrafts missiles or official satellites. It can determine the direction, distance, height and speed of objects that are not visible to the human eyes.

Application– Radar has a large variety of applications involving precise measurements of distances. Besides being used for navigating ships and aircrafts it is used for mapping stars and other meteorological disturbances, and studying planets and their moons or satellites. It is used for determining altitudes, aeroplane navigating in fogs and in the dark. A useful application of radar is for police speed trap. Here a special radar device is used which responds differently to the reflections from moving objects and stationary objects.

SONAR — Acronym for Sound Navigation and Ranging (SONAR)—a technique and apparatus for determining the location of an object by reflected sound-waves. In fact it is a system for detecting and locating submerged objects or communication underwater by transmitting high frequency sound wave and collecting the reflected wave. The Sonar principle is used to determine the depth of shallow bodies of water and to locate fish under water submarines. Initially developed as a military instrument for locating submarines, it is widely used for measuring water depth and in Arctic regions for measuring ice-thickness.

In Active Sonar pulses of high frequency (high pitched) sounds are beamed downwards and at angles from the bottom of a ship. The echoes are received by an apparatus that measures the time interval, then computers the distance and frictions of the reflecting object. This information is shown on a dial, or plotted automatically on a chart. Passive Sonar does not send out sounds. It detects sounds made by submarine engines or other sound producing objects.

Essay No. 02

Science in The Service of Man

Science has opened and enlarged new frontiers of human knowledge, information, achievement, comforts and conveniences. Now we have a window, large enough to peep into the hitherto unknown, dark and mysterious areas of nature in the form of modern science. This passage from ignorance to knowledge, from darkness to light, from superstitions and blind beliefs to scientific temper and rationality, has been a long struggle, full of strife, labour, sweat and challenges. But it is man’s nature to seek and face challenges and his destiny to overcome them.

Man’s endless thirst for knowledge and conquest has resulted in phenomenal advancement of science in each and every walk of life and so the modern age has rightly been christened as the Age of Science. Science means reasoning, analysis, objectivity and systematic study4of things. Science is very comprehensive, universal, all-inclusive, simple and yet very complex and so beyond the approach of a satisfying definition. It may not be defined but touches all of us at all the places and times. Its expression is universal, unambiguous and palpable and well understood by the educated people in most of the cases. People know that science has helped man to conquer time and space and the world has turned into a global village. Now, the moon is in the palm of his hand and planets are not too far off for his scrutiny and study. We have supersonic planes and will soon have hypersonic planes to enable us cover the distance between Tokyo and New York in just 2 hours. Satellite communication has ushered in instantaneous contact from one corner of the globe to another. Instant communication through cordless, cellular and mobile telephones, paging, and electronic mail, etc. are really wonderful. Then there are computers, which help retrieve any information you require from anywhere in the world. Satellites have also revolutionised our world of entertainment through dish and cable T.V. Science has completely changed the face of the earth and the outlook of man. So much so that if one of our forefathers were to come alive, he would not easily recognize either the place or his descendants. And the march along the path of progress, past milestones of achievements, is on in the vehicle of science. The ride is so wonderful, so pleasant and thrilling that it makes one forget his vital breath for a moment.

Life has become so easy, convenient and comfortable because of our scientific achievements. Science is a powerful weapon and it is up to man how he uses it. Science is neither a blessing nor a curse in itself. It is knowledge—pure, powerful, universal and absorbing—always at our service, command and bidding. Its aim is to serve sincerely but it is our prerogative to decide what service we ask science to render. Therefore, it is unwise to categorise science as evil or good.

Science has helped us in eradicating many diseases, which were fatal in the past, and in treating many others. Now transplantation of many vital organs is a common medical practice. As a result of many medical discoveries and inventions, man finds himself more safe, secure and his age lengthened. It is because of many scientific teachings and learning-aids that distant education is so popular, cheap and universal. Science has turned learning into a pleasure.

The wonders and achievements of science are too many. Take for example, the harnessing of nuclear energy. It has broadened the horizons of power to be used to run mills, factories, engines, railways, to light up homes and streets, to energise pump sets and tube wells, to smoothen earth-moving and mining work, to be used in irradiation, to preserve seafood and other food items and sterilization of medicines, to name only a few of the areas. There are many other areas which have immensely benefited by it. It is a great and inexhaustible power with huge potentialities.

Again, the world of scientific appliances is no less wonderful. Now man has more time because of these gadgets and conveniences. Science has helped man to leapfrog into a new, bold and wonderful world of fantastic achievements, comforts and conveniences. No doubt, the other side of the coin shows the darker visage of science. The misuse of science and its inventions has brought the entire humanity on the brink of destruction and annihilation. It has produced very dangerous weapons, like nuclear bombs, missiles, and fatal and poisonous nerve gases, etc., but again it needs to be underlined that science is neither good nor bad. It is knowledge; it is power, a boon and gift, a key to unlock the secrets of nature. If we misuse it, we are to blame.

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Essay on "Science in The Service of Man" for School, College Students
Science is a powerful weapon and it is up to man how to uses it. It is neither a boon nor a curse. However, it is in the hands of man to decide what service he desires from science. Thus, it is unwise to categories science as an evil or good. Science is a knowledge, a power, a blessing and a key to solve the different secrets of nature.
Essay on Science in the Service of Man for Students
( Essay-3 ) Science in the Service of Man Essay 1500 words. Introduction: Science, with its myriad branches and applications, stands as one of humanity's most remarkable endeavors. Science, a systematic pursuit of knowledge, has been instrumental in shaping civilization. From ancient times to the modern era, science has served humanity in ...
Science in the Service of Man Essay with Quotations
Short Essay on Science in the Service of Man for Class 10, Class 12, F.A, FSC, B.A, BSC and Graduation. Science is an unending search for truth. It has proved a faithful friend of mankind. It has increased human comfort. Life is a struggle. The man has to work throughout his life. It is the science that helps him to make a safe home for him.
3
This essay is based on a talk given at the opening ceremony of the conference "Science in the Service of Mankind," Vienna, Austria, July 8-14, 1979. The scientific optimist who wrote in the 1808 Elements of Natural Philosophy: "The great object of science is to ameliorate the condition of man, by adding to the advantages which he ...
English Essay on "Science in The Service of Man ...
English Essay on "Science in The Service of Man" complete Paragraph and Speech for School, College Students, essay for Class 8, 9, 10, 12 and Graduation. About. Vision; ... Science in The Service of Man . Or . Science and Human Happiness . Science is the greatest servant of man today. It is the Alladin's Lamp and it hides a Jinn who does ...
Essay On Science In The Service Of Man
Science is a powerful weapon and it is up to man how to uses it. It is neither a boon nor a curse. However, it is in the hands of man to decide what service he desires from science. Thus, it is unwise to categories science as an evil or good. Science is a knowledge, a power, a blessing and a a key to solve the different secrets of nature.
Science in the Service of Man
Science in the Service of Man | English Essay. Albert Einstein, a German-born U.S. physicist says: Knowledge resembles a statue of marble which stands in the desert and is continuously threatened with burial by the shifting sands. The hands of science must ever be at work in order that the marble column continues everlastingly to shine in the sun.
An Ideal of Service to Our Fellow Man
An Ideal of Service to Our Fellow Man From 1954, Nobel Prize-winning physicist Albert Einstein finds beauty in life's mysteries, and says the fate of mankind depends on individuals choosing public ...
Essay on "Science in the Service of Man" for School, College Students
Science in the Service of Man . Science has rendered a great service to man by exposing the hollowness of several superstitious beliefs and myths, which stifled man's onward march to progress. Illness was attributed to sorcery, failure of crops -to-angry gods or malignant demons.
English Essay on "Science in The Service of Man" English Essay
Science in The Service of Man. Essay No. 01. Science has brought a transformation in the man's entire lifestyle. We do every work with the help of science. Even the most ordinary things we use in this modern age is the result of invention of science. A lead pencil, a pen or a book is the product of science. Science has conquered time and ...
Essay on Science In The Service of Man
Essay on Science In The Service of Man: Science has revolutionized the way we live our lives, making it easier, faster, and more convenient. From medical advancements to technological innovations, science has truly been in the service of man. In this essay, we will explore the various ways in which science has improved our lives and how it ...
Science in the Service of Mankind
It is a matter, perhaps, of training, rience, of the time when the two areas are first brought to concern of the young man or woman who is being trained, haps, in addition, of a variety of factors that we do not yet stand. 192 Volume XXVIII April 1966 Number 2. SCIENCE IN THE SERVICE OF MANKIND 77.
PDF SCIENCE AND TECHNOLOGY IN THE SERVICE OF MAN
science and technology that have dealt seriously with the mode of living in the society. Thus, this essay seeks to explore the historical development of science and technology, its glories and
Science in the service of man
The document discusses three solutions to overpopulation: 1) Relocation and exploration, which involves finding new places for humans to live to gain more resources and space; 2) Management of birth rates, such as employing birth limits like a one-child policy to control population growth; 3) Decimation of the human population by selecting and ...
Science Is The Service Of Man (Essay Sample)
Science is the service of man in many terms such as in education, health, and technology. Education is an essential part of social system because it enables the young ones gain learning and proper training in order to engage to the problem that the communities are facing. The role of science in education system kicks-in in the form of academic ...
Science in Service of Man Essay
Science in service of man Essay - Free download as PDF File (.pdf), Text File (.txt) or read online for free. 1) Science is a systematically organized body of knowledge that has allowed mankind to evolve from cave dwellers to modern humans through discoveries like fire, agriculture, and electricity. 2) Major scientific achievements that have improved life include technologies like the ...
SCIENCE AND TECHNOLOGY IN THE SERVICE OF MAN
1. SCIENCE AND TECHNOLOGY IN THE SERVICE OF MAN. Abstract: The m an of today has conquered his environment with vast intellectual abilities and overwhelming. expertise. With his genius as homo ...
BIOLOGY IN THE SERVICE OF MAN
Progress in biological understanding has proceeded at a spectacular rate for two decades. The deepening insights into the nature of man and his diverse living kin could well be reward enough for the large investment of effort and funds. Such understanding is more than a highlight of our culture; it is a primary tool of our working civilization. In the pages that follow we shall seek to ...
ASL Topic n Short Essays with Example on
ASL Topic n Short Essays with Example on - Science in the Service of Man. (The following speech is perfect for 1 min. to 1.05 min) The first scientist was the caveman who picked up a stone to kill a deer- he made something to serve his purpose. Science made advancement in the sharpening of stones to serve as weapons, making fire by striking ...
Essay, Paragraph or Speech on "Science in the Service of Man" Complete
Essay No. 02 . Science in The Service of Man . Science has opened and enlarged new frontiers of human knowledge, information, achievement, comforts and conveniences. Now we have a window, large enough to peep into the hitherto unknown, dark and mysterious areas of nature in the form of modern science. This passage from ignorance to knowledge ...
Science in the Service of Man essay. Lecture:68 pms
Here I have explained the topic "Science in the Service of Man" Peshawar Model school
6. Science in the the Service of Man Essay |Golden Essays ...
#essay #science #scieceintheserviceofmanessay #benefitsofscience2nd year English is a lengthy and comprehensive section. So, it is better to memorize all pas...

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SCIENCE AND TECHNOLOGY IN THE SERVICE OF MAN

The Life Sciences: Recent Progress and Application to Human Affairs: The World of Biological Research Requirements for the Future.

CHAPTER TWO BIOLOGY IN THE SERVICE OF MAN

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